Abstract:
INTRODUCTION:The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB) limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT) plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS:Contrast-enhanced magnetic resonance imaging (MRI) and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS:Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR-HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS:Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Murrell DH,Zarghami N,Jensen MD,Chambers AF,Wong E,Foster PJdoi
10.1016/j.tranon.2016.04.006subject
Has Abstractpub_date
2016-06-01 00:00:00pages
219-27issue
3issn
1936-5233pii
S1936-5233(16)30025-0journal_volume
9pub_type
杂志文章abstract::Tyrosine kinase inhibitors (TKIs) provide clinical benefits to the lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, non-invasively determine EGFR mutation status in patients before targeted therapy remains a challenge. This study aimed to develop and validate a nomogram for preoper...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100954
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abstract::The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most altered in cancer, leading to a range of cellular responses including enhanced proliferation, survival, and metabolism, and is thus an attractive target for anticancer drug development. Stimulation of the PI3K pathway can be initiated by alterat...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.11118
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abstract::This study aimed to identify the biological processes associated with long-term survival in high-grade serous ovarian cancer (HGSOC). HGSOC cases obtained from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) database were divided into long-term survivors (LTS) and normal-term survivors (NTS) based on survival cutoffs...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100885
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abstract::Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA) levels and digital rectal examination. A decisive diagnosis of PCa is based on pr...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2016.05.004
更新日期:2016-08-01 00:00:00
abstract::Checkpoint with FHA and RING finger domains (CHFR) was first recognized as an early mitotic checkpoint protein that delayed the cell cycle in response to microtubule-targeting drugs. It is an E3 ubiquitin ligase that ubiquitinates target proteins to direct them to the proteasome for degradation or to alter their activ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.08109
更新日期:2008-07-01 00:00:00
abstract:PURPOSE:In gastric adenocarcinoma (GC), the major tumor suppressor genes (TSGs) such as p16, PTEN, Rb, E-cadherin, and p53, may play important roles in various regulatory pathways and in tumor suppression. This study evaluated the loss of heterozygosity (LOH) of microsatellite and protein expression of 5 TSGs and the r...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.10.007
更新日期:2018-02-01 00:00:00
abstract::Tumor cells grow in nutrient- and oxygen-deprived microenvironments and adapt to the suboptimal growth conditions by altering their metabolic pathways. This adaptation process commonly results in a tumor phenotype that displays a high rate of aerobic glycolysis and aggressive tumor characteristics. The glucose regulat...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.11319
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND AND AIM:Desmoplasia is a characteristic feature and a suspected mechanism of tumor progression in pancreatic ductal adenocarcinoma (PDAC). Main constituents of the stroma involve cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM). The aim of this study was to dissect the interaction of CAFs,...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.04.009
更新日期:2017-08-01 00:00:00
abstract::Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibitors and chemothera...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100987
更新日期:2021-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.08145
更新日期:2008-09-01 00:00:00
abstract::Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.04.013
更新日期:2018-08-01 00:00:00
abstract::Peritoneal carcinomatosis (PC) of colorectal origin is associated with a poor prognosis. However, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is available for a selected group of PC patients, which significantly increases overall survival rates up to 30%. As a consequence, there is su...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.10220
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:Regional lymph node (LN) metastasis is a strong and well-established prognostic factor in colon cancer, and recent data suggest a prognostic value of detecting micrometastases and isolated tumor cells in regional LNs. The aim of the study was to investigate the clinical relevance of detecting sentinel lymph ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.01.015
更新日期:2018-04-01 00:00:00
abstract::Clinical trials using anti-vascular endothelial growth factor /(VEGF) molecules induce a modest improvement in overall survival, measurable in weeks to just a few months, and tumors respond differently to these agents. In this review article, we have exposed some tumor characteristics and processes that may impair the...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2019.04.022
更新日期:2019-07-01 00:00:00
abstract::Breast cancer is the second leading cause of cancer death in women worldwide. Incurable metastatic breast disease presents a major clinical challenge and is the main cause of breast cancer-related death. The epithelial-mesenchymal transition (EMT) is a critical early promoter of metastasis. In the present study, we id...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.07.015
更新日期:2018-10-01 00:00:00
abstract::Insufficient delivery of systemically administered anticancer drugs to tumors can compromise therapeutic efficacy and develop drug delivery-based therapeutic resistance. Nanotherapeutics such as PEGylated liposomal doxorubicin (PLD) are designed to preferentially accumulate in tumors utilizing enhanced permeation and ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.05.011
更新日期:2019-09-01 00:00:00
abstract::This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. Twenty-five consecutive patients who had metastatic or unresectable RCC treated with anti-PD-1 therapy we...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100918
更新日期:2021-01-01 00:00:00
abstract:PURPOSE:In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to conf...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.08.007
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy. PATIENTS AND METHODS:Genomic profiles of patients with advanced sarcoma included in the ProfiLER progr...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100870
更新日期:2020-12-01 00:00:00
abstract:INTRODUCTION:In ovarian cancer, new therapeutic strategies are needed because the vast majority of patients develop a recurrence and resistance to platinum derivates. Attached to the AGO-OVAR2.11 study investigating the multityrosine kinase inhibitor sunitinib in recurrent platinum refractory ovarian cancers, this tran...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13205
更新日期:2013-06-01 00:00:00
abstract::Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC) is currently an urgent need in oncology. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. A new compound based on the benzothiophene nucleus...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.04.005
更新日期:2019-07-01 00:00:00
abstract::Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.11.011
更新日期:2016-02-01 00:00:00
abstract::Gastrointestinal stromal tumors (GISTs) are potentially malignancies that can occur anywhere in the digestive tract. Tyrosine kinase inhibitors (TKIs) such as imatinib have proven effective since the discovery of KIT and PDGFRA. The current version of NCNN, ESMO and EURACAN guidelines recognized that the three main pr...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2020.100812
更新日期:2020-10-01 00:00:00
abstract:OBJECTIVE:Primary hepatic lymphoma (PHL) is a rare malignancy with lesions confined to the liver. It is characterized by a large number of monomorphic, medium-sized lymphocytic infiltrates in the hepatic sinusoid. Due to the rarity of this malignancy, our current understanding of PHL is limited. METHODS:We collected i...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100931
更新日期:2021-01-01 00:00:00
abstract::BRAFV600-mutated colorectal cancer (CRC) accounts for 8% to 12% of all CRC diagnoses. These tumors are often associated with specific patient features, including right-sided primary tumor location, peritoneal and non-regional lymph node involvement, and poor prognosis. In approximately 30% of cases, a simultaneous mis...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2020.100795
更新日期:2020-09-01 00:00:00
abstract:PURPOSE:In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS:We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuv...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.07.005
更新日期:2014-10-24 00:00:00
abstract::The presence of circulating tumor cells (CTCs) in the blood of cancer patients may guide the use of therapy. We investigated how to evaluate a reduction in the number of CTCs after administration of therapy. CTCs were enumerated with the CellSearch system in 111 metastatic breast and 185 metastatic prostate cancer pat...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.12247
更新日期:2012-12-01 00:00:00
abstract::ErbB-3 (HER-3) receptor is involved in tumor progression and resistance to therapy. Development of specific inhibitors impairing the activity of ErbB-3 is an attractive tool for cancer therapeutics. MP-RM-1, a murine monoclonal antibody targeting human ErbB-3, has shown anticancer activity in preclinical models. With ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13475
更新日期:2013-12-01 00:00:00
abstract::Programmed cell death-ligand 2 (PD-L2) is one of the two ligands of the programmed cell death-1 (PD-1) receptor, an inhibitory protein mainly expressed on activated immune cells that is targeted in the clinic, with successful and remarkable results. The PD-1/PD-Ls axis was shown to be one of the most relevant immunosu...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2020.100811
更新日期:2020-10-01 00:00:00
abstract::Elderly patients with esophageal carcinoma may benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen has not been determined. The aim of our study was to assess the efficiency and tolerance of treatment with a concurrent 5-fluorouracil (5-Fu)-based regimen and a taxane-...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.12.008
更新日期:2020-03-01 00:00:00