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 therapeutic ratio. We sought to translated these preclinical findings to a phase I trial. METHODS:Twenty-five patients with non-resectable HNC were scheduled to receive gemcitabine twice weekly during the last 2 weeks (total 5 infusions) of hyperfractionated radiotherapy delivering 1.2 Gy twice daily to total 76.8 Gy. Tumor biopsies to measure active intracellular (phosphorylated) gemcitabine were planned after the first drug delivery. Patients were assigned to escalating dose cohorts using the Continuous Reassessment Method. RESULTS:Twenty-one patients evaluable for toxicity were divided into cohorts receiving twice weekly treatment with 10, 20, 33, or 50 mg/m(2) gemcitabine. Dose-limiting toxicity was grade 3-4 confluent mucositis/pharyngitis, and the maximally tolerated dose (MTD) was 20 mg/m(2). Median survival was 20 months, with no difference between cohorts receiving lower (10, 20 mg/m(2)) or higher (33, 50 mg/m(2)) gemcitabine doses. Tumor biopsies after the first drug delivery showed only a minority of tumor cells in the specimens. CONCLUSION:These findings validate preclinical models that show that gemcitabine is radiation sensitizer at doses far below those used for systemic chemotherapy. However, the improvement in the therapeutic ratio predicted from the preclinical study did not translate into a substantial relative increase in the MTD of the drug in the clinical phase I trial.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Popovtzer A,Normolle D,Worden FP,Prince ME,Chepeha DB,Wolf GT,Bradford CR,Lawrence TS,Eisbruch Adoi
10.1016/j.tranon.2014.04.016subject
Has Abstractpub_date
2014-08-01 00:00:00pages
479-83issue
4issn
1936-5233pii
S1936-5233(14)00051-5journal_volume
7pub_type
杂志文章abstract:OBJECTIVES:Recurrence of hepatocellular carcinoma can arise from the primary tumor ("early recurrence") or de novo from tumor formation in a cirrhotic environment ("late recurrence"). We aimed to develop one simple gene expression score applicable in both the tumor and the surrounding liver that can predict the recurre...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.02.003
更新日期:2016-04-01 00:00:00
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
更新日期:2021-01-01 00:00:00
abstract:OBJECT:Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. METHODS:MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.02.004
更新日期:2018-04-01 00:00:00
abstract:OBJECT:Thyroid cancer represents the most frequent malignancy of the endocrine system with an increasing incidence worldwide. Novel imaging techniques are able to further characterize tumors and even predict histopathology features. Texture analysis is an emergent imaging technique to extract extensive data from an rad...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.09.003
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:The present study compared the effect of combination therapy using human apolipoprotein(a) kringle V (rhLK8) to conventional chemotherapy with paclitaxel for human ovarian carcinoma producing high or low levels of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS:Human ovarian carcinoma cel...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.04.005
更新日期:2014-06-17 00:00:00
abstract::Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effec...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.04.014
更新日期:2014-05-12 00:00:00
abstract:BACKGROUND:Head and neck squamous cell carcinomas (HNSC) are among the most common malignant tumors with high incidence, relapse, and mortality rate. STAT proteins are implicated in various biological processes, including cell proliferation, metastasis, and immune regulation. METHOD:Various bioinformatics tools were u...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100976
更新日期:2021-01-01 00:00:00
abstract::We study the reproducibility of quantitative imaging features that are used to describe tumor shape, size, and texture from computed tomography (CT) scans of non-small cell lung cancer (NSCLC). CT images are dependent on various scanning factors. We focus on characterizing image features that are reproducible in the p...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13844
更新日期:2014-02-01 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:PURPOSE:To prospectively investigate ultrasound-guided diffuse optical tomography (US-guided DOT) in predicting breast cancer response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS:Eighty-eight breast cancer patients, with a total of 93 lesions, were included in our study. Pre- and post-last chemotherapy, s...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.10.011
更新日期:2018-02-01 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::Breast cancer is the most common malignancy in women worldwide, with a developmental process spanning decades. The malignant cells recruit a variety of cells including fibroblasts, endothelial cells, immune cells, and adipocytes, creating the tumor microenvironment. The tumor microenvironment has emerged as active par...
journal_title:Translational oncology
pub_type: 杂志文章,评审
doi:10.1016/j.tranon.2017.12.009
更新日期:2018-04-01 00:00:00
abstract::Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch t...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.07.004
更新日期:2014-10-24 00:00:00
abstract::Many human malignancies require extracellular arginine (Arg) for survival because the key enzyme for de novo Arg biosynthesis, argininosuccinate synthetase 1 (ASS1), is silenced. Recombinant arginine deiminase (ADI-PEG20), which digests extracellular Arg, has been in clinical trials for treating ASS1-negative tumors. ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.12.003
更新日期:2020-02-01 00:00:00
abstract::Bone is one of the most frequent metastatic sites in non-small cell lung cancer (NSCLC). Osimertinib, with and without bevacizumab (BV), has been investigated on advanced NSCLC patients. However, the efficacy of those drugs on bone metastasis of NSCLC has not been investigated. The human NSCLC cell line H1975, express...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100826
更新日期:2020-10-01 00:00:00
abstract::Multiple myeloma (MM) is a very heterogeneous disease, characterized by multiple cytogenetic aberrations on plasma cells (PC) that have been traditionally used to predict the outcome of the disease. A mayor issue on the analysis of PC is the sometimes low infiltration of these cells in the bone marrow that hampers cyt...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.02.021
更新日期:2018-06-01 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::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: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::Intestinal commensal bacteria have recently been shown to trigger macrophages to produce diffusible clastogens (or chromosome-breaking factors) through a bystander effect (BSE) that mediates DNA damage and induces chromosomal instability in neighboring cells. Colon macrophages appear central to colon carcinogenesis an...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13412
更新日期:2013-10-01 00:00:00
abstract:OBJECTIVE:The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS:Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and fi...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2016.12.006
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Oral squamous cell carcinoma (OSCC) remains a challenging cancer to treat despite all the advances of the last 50 years. Kallikrein 5 (KLK5) is among the serine proteases implicated in OSCC development. However, whether the activity of KLK5 promotes carcinogenesis is still controversial. Moreover, knowledge ...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100970
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:Hepatitis B virus (HBV) is one of the most prominent risk factors for hepatocellular carcinoma (HCC) development and virus-mediated cases represents more than 80% of HCC in East Asia, where it is endemic. Currently, the HBV status of pathological HCC is not fully clarified, especially by comparison to nontum...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.05.006
更新日期:2019-09-01 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::CAP2 has been suggested as a potential diagnostic biomarker for early hepatocellular carcinoma (HCC). However, its prognostic significance in HCC remains unclear. Here, we show that CAP2 expression is much higher in HCC tissues than that in paracarcinoma tissues, at both mRNA and protein levels. Data of immunohistoche...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.08.003
更新日期:2015-10-01 00:00:00
abstract::Hormone receptor positive (HR+) breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.04.011
更新日期:2017-08-01 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::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::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::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