Abstract:
:Chronic myelogenous leukemia (CML) can be controlled for years with the tyrosine kinase inhibitor imatinib but because imatinib poorly penetrates the blood-brain barrier (BBB), on occasion, the CML clone will thrive and evolve to an accelerated phase in the resulting imatinib sanctuary within the central nervous system. In this, CML resembles glioblastoma in that imatinib, which otherwise may be effective, cannot get to the tumor. Although a common street drug of abuse, methamphetamine is Food and Drug Administration-approved and marketed as a pharmaceutical drug to treat attention-deficit disorders. It has shown the ability to open the BBB in rodents. We have some clinical hints that it may do so in humans as well. This short note presents three new points potentially leading to better tyrosine kinase inhibition behind the BBB: 1) Pharmaceutical methamphetamine may have a useful role in treating both CML and glioblastoma by allowing higher imatinib concentrations behind the BBB. 2) The old antidepressant and monoamine oxidase inhibitor selegiline, used to treat Parkinson disease, is catabolized to methamphetamine. Selegiline, as a nonscheduled drug,may therefore be an easier way to open the BBB, allowing more effective chemotherapy with tyrosine kinases. 3) Dasatinib is a tyrosine kinase inhibitor with a spectrum of inhibition only partially overlapping that of imatinib and a mechanism of tyrosine kinase inhibition that is different from that of imatinib. The two should be additive. In addition, dasatinib crosses the BBB poorly, and it can therefore be expected to benefit from methamphetamine-assisted entry.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Kast RE,Focosi Ddoi
10.1593/tlo.09280subject
Has Abstractpub_date
2010-02-01 00:00:00pages
13-5issue
1issn
1936-5233journal_volume
3pub_type
杂志文章abstract:BACKGROUND:Immunotherapy using dendritic cell (DC) vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS:We engineered Lewis lung cancer cells (LLCs) and bone marrow-derived DCs to express tumor-associated antigen (TAA) ovalbumin (OVA) via lentiviral vector plasmid encoding OVA gene. We then ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.12.002
更新日期:2017-04-01 00:00:00
abstract::The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects. Among these mechanisms of action, ATO has been shown to cause acute vascular shutdown and massive tumor necrosis in a murine solid tumor m...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.12322
更新日期:2013-02-01 00:00:00
abstract::Glioblastoma (GBM) with oligodendroglioma component (GBMO) is a newly described GBM subtype in the 2007 World Health Organization classification. However, its biological and genetic characteristics are largely unknown. We investigated the clinicopathological and molecular features of 34 GBMOs and compared the survival...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.10.002
更新日期:2014-12-01 00:00:00
abstract::Monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small ce...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100865
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Once-weekly gemcitabine concurrent with radiotherapy was highly effective in the treatment of head and neck cancer (HNC) but limited by high mucosal toxicity. Pre-clinical investigations suggested that delivering gemcitabine at substantially lower doses twice weekly during radiotherapy improved the therapeut...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.04.016
更新日期:2014-08-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.08.002
更新日期:2018-12-01 00:00:00
abstract::Acquired uniparental disomy (aUPD) regions pinpoint homozygousity and monoallelic expressed genes. We analyzed The Cancer Genome Atlas single-nucleotide polymorphism arrays and expression data from oral cavity, oropharynx, and larynx cancers to identify frequency of aUPD in each tumor type and association of aUPD regi...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100763
更新日期:2020-05-01 00:00:00
abstract::High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a "nanoimmunotherapy," which combines photothermal therapy (PTT) using CpG oligodeoxynucl...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100823
更新日期:2020-10-01 00:00:00
abstract::Accumulating evidence indicates that CDK2 promotes hyperproliferation and is associated to poor prognosis in multiple cancer cells. However, the physiological role of CDK2 in GBM and the biological mechanism still remains unclear. In this study, we identified that CDK2 expression was significantly enriched in GBM tumo...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.08.007
更新日期:2016-12-01 00:00:00
abstract::Wnt signaling has been implicated as a driver of prostate cancer-related osteoblast differentiation, and previous studies have linked modifications in Wnt function with the induction of tumor metastasis. A unique aspect of prostate cancer bone metastases in mouse models is their relative predilection to the hindlimb (...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100747
更新日期:2020-04-01 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::Therapy-induced senescence (TIS), a cytostatic stress response in cancer cells, is induced inefficiently by current anticancer agents and radiation. The mechanisms that mediate TIS in cancer cells are not well defined. Herein, we characterize a robust senescence response both in vitro and in vivo to the quinone diaziq...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.12181
更新日期:2012-08-01 00:00:00
abstract::A targeted and timely offered treatment can be a benefitting tool for patients with acute promyelocytic leukemia (APML). Current round of study made use of potential morphological and immature fraction-related parameters (cell population data) generated during complete blood cell count (CBC), through artificial neural...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.09.009
更新日期:2020-01-01 00:00:00
abstract::Ovarian cancer remains the most frequently lethal of the gynecologic cancers owing to the late detection of this disease. Here, by using human specimens and three mouse models of ovarian cancer, we tested the feasibility of nonlinear imaging approaches, the multiphoton microscopy (MPM) and second harmonic generation (...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.09310
更新日期:2010-06-01 00:00:00
abstract::The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO+) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO+ that were e...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.06.002
更新日期:2016-08-01 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:BACKGROUND:An elevated preoperative C-reactive protein/albumin (CRP/Alb) ratio has been reported to be associated with a poor prognosis for hepatocellular carcinoma. The aim of the present study was to investigate the prognostic value of the preoperative CRP/Alb ratio and compare it with other systemic inflammatory res...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.06.006
更新日期:2015-08-01 00:00:00
abstract:PURPOSE:To evaluate whether contrast enhancement on cone-beam breast-CT (CBBCT) could aid in discrimination of breast cancer subtypes and receptor status. METHODS:This study included female patients age >40 years with malignant breast lesions identified on contrast-enhanced CBBCT. Contrast enhancement of malignant bre...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.08.010
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:To determine the accuracy of a handheld ultrasound-guided optoacoustic tomography (US-OT) probe developed for human deep-tissue imaging in ex vivo assessment of tumor margins postlumpectomy. METHODS:A custom-built two-dimensional (2D) US-OT-handheld probe was used to scan 15 lumpectomy breast specimens. Optoac...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.11.005
更新日期:2020-02-01 00:00:00
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
更新日期:2021-01-01 00:00:00
abstract::This article describes methods and issues that are specific to the assessment of change in tumor characteristics as measured using quantitative magnetic resonance (MR) techniques and how this relates to the establishment of quantitative MR imaging (MRI) biomarkers of patient response to therapy. The initial focus is o...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.09241
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND AND STUDY AIM:To develop a molecular imaging endoscopic system that eliminates tissue autofluorescence and distinguishes multiple fluorescent markers specifically on the cancerous lesions. METHODS:Newly developed multi-spectral fluorescence endoscope device has the potential to eliminate signal interference...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.10.006
更新日期:2019-02-01 00:00:00
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
更新日期:2011-08-01 00:00:00
abstract::Past studies have shown that the inositol polyphosphate 5-phosphatase, phosphatidylinositol 4,5-bisphosphate 5-phosphatase (PIB5PA), is commonly downregulated or lost in melanomas, which contributes to elevated activation of phosphatidylinositol 3-kinase (PI3K)/Akt in melanoma cells. In this report, we provide evidenc...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13277
更新日期:2013-08-01 00:00:00
abstract::Distinguishing synchronous and metachronous primary lung adenocarcinomas from adenocarcinomas with intrapulmonary metastasis is essential for optimal patient management. In this study, multiple lung adenocarcinomas occurring in the same patient were evaluated using comprehensive histopathologic evaluation supplemented...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.02.009
更新日期:2017-06-01 00:00:00
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...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.04.006
更新日期:2016-06-01 00:00:00
abstract::Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane receptor tyrosine kinase involved in the development and progression of cancer whose activation strongly promotes cell growth and survival. IGF-1R exerts its main actions through the activation of the mitogen-activated protein kinase and phosphoinositid...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.11265
更新日期:2012-02-01 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:PURPOSE:This study presented a three-dimensional magnetic resonance (MR)-based method to separate a breast into four quadrants for quantitative measurements of the quadrant breast volume (BV) and density. METHODS:Breast MR images from 58 healthy women were studied. The breast and the fibroglandular tissue were segment...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.04.005
更新日期:2015-08-01 00:00:00
abstract::Studies investigating dynamic susceptibility contrast magnetic resonance imaging-determined relative cerebral blood volume (rCBV) maps as a metric of treatment response assessment have generated conflicting results. We evaluated the potential of various analytical techniques to predict survival of patients with glioma...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13670
更新日期:2013-12-01 00:00:00