RRx-001, an epigenetic-based radio- and chemosensitizer, has vascular normalizing effects on SCCVII and U87 tumors.


BACKGROUND:The tumor-specific microregional effects of the anticancer agent RRx-001, a novel epigenetic-based radio/chemosensitizer with nitrogen oxide-donating properties in phase II clinical trials, were investigated with whole tissue section quantitative immunohistological staining in mouse SCCVII and human U87 tumors. RESULTS:SCCVII tumors exhibited regions of intermittent perfusion exemplified by co-localization of vessels with the hypoxia marker pimonidazole commonly occurring throughout the tissue. A moderate increase in perfusion (21 to 28 %) was observed after a bolus dose of the perivascular stain DiOC7(3), however, with the absence of an increase in tissue oxygenation. U87 tumors showed an absence of blood flow over large areas of treated tumors after dosing with RRx-001. However, these areas did not become necrotic and returned to near normal levels after 12 h. No significant change in tumor hypoxia was seen at 90 min or 12 h. For both tumor types, RRx-001 treatment resulted in the loss of perfusion in the large regions of the tumor; however, at the 12-h time point, both tumor types showed an increase in vessel perfusion but no significant decrease in hypoxia. CONCLUSIONS:These data suggest a redistribution of blood flow within the tumor for both tumor types akin to vascular normalization. Differences between the tumors were related to tumor architecture and distribution of alpha-smooth muscle actin (α-SMA). RRx-001 shows promise for short-term blood flow redistribution in tumors with a pericyte- and α-SMA-rich vasculature. Expression of α-SMA in tumor vasculature could therefore be useful for predicting tumor response to RRx-001.


Clin Epigenetics


Clinical epigenetics


Oronsky B,Scicinski J,Cabrales P,Minchinton A




Has Abstract


2016-05-11 00:00:00












  • Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma.

    abstract:BACKGROUND:Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagn...

    journal_title:Clinical epigenetics

    pub_type: 临床试验,杂志文章


    authors: Henriksen SD,Madsen PH,Larsen AC,Johansen MB,Drewes AM,Pedersen IS,Krarup H,Thorlacius-Ussing O

    更新日期:2016-11-16 00:00:00

  • Alternative methylation of intron motifs is associated with cancer-related gene expression in both canine mammary tumor and human breast cancer.

    abstract:BACKGROUND:Canine mammary tumor (CMT) has long been considered as a good animal model for human breast cancer (HBC) due to their pathological and biological similarities. However, only a few aspects of the epigenome have been explored in both HBC and CMT. Moreover, DNA methylation studies have mainly been limited to th...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Nam AR,Lee KH,Hwang HJ,Schabort JJ,An JH,Won SH,Cho JY

    更新日期:2020-07-21 00:00:00

  • Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health.

    abstract:BACKGROUND:Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic hea...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Tsai PC,Glastonbury CA,Eliot MN,Bollepalli S,Yet I,Castillo-Fernandez JE,Carnero-Montoro E,Hardiman T,Martin TC,Vickers A,Mangino M,Ward K,Pietiläinen KH,Deloukas P,Spector TD,Viñuela A,Loucks EB,Ollikainen M,Kelsey K

    更新日期:2018-10-20 00:00:00

  • MUC1 is associated with TFF2 methylation in gastric cancer.

    abstract:BACKGROUND:Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1-/- mice compared with controls. However, little is known of the molecul...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Ge Y,Ma G,Liu H,Lin Y,Zhang G,Du M,Wang M,Chu H,Zhang H,Zhang Z

    更新日期:2020-03-02 00:00:00

  • Correction to: DNA methylation signature is prognostic of choroid plexus tumor aggressiveness.

    abstract::After publication of the original article [1], authors have requested to add a 'J' as middle name for Richard Gilbertson. Hence, full name should be Richard J Gilbertson. ...

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    pub_type: 已发布勘误


    authors: Pienkowska M,Choufani S,Turinsky AL,Guha T,Merino DM,Novokmet A,Brudno M,Weksberg R,Shlien A,Hawkins C,Bouffet E,Tabori U,Gilbertson RJ,Finlay JL,Jabado N,Thomas C,Sill M,Capper D,Hasselblatt M,Malkin D

    更新日期:2019-10-21 00:00:00

  • Comprehensive evaluation of targeted multiplex bisulphite PCR sequencing for validation of DNA methylation biomarker panels.

    abstract:BACKGROUND:DNA methylation is a well-studied epigenetic mark that is frequently altered in diseases such as cancer, where specific changes are known to reflect the type and severity of the disease. Therefore, there is a growing interest in assessing the clinical utility of DNA methylation as a biomarker for diagnosing ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Lam D,Luu PL,Song JZ,Qu W,Risbridger GP,Lawrence MG,Lu J,Trau M,Korbie D,Clark SJ,Pidsley R,Stirzaker C

    更新日期:2020-06-22 00:00:00

  • Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellu

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    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Leung KL,Sanchita S,Pham CT,Davis BA,Okhovat M,Ding X,Dumesic P,Grogan TR,Williams KJ,Morselli M,Ma F,Carbone L,Li X,Pellegrini M,Dumesic DA,Chazenbalk GD

    更新日期:2020-11-23 00:00:00

  • Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer.

    abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Boughanem H,Cabrera-Mulero A,Hernández-Alonso P,Clemente-Postigo M,Casanueva FF,Tinahones FJ,Morcillo S,Crujeiras AB,Macias-Gonzalez M

    更新日期:2020-06-09 00:00:00

  • T cell epigenetic remodeling and accelerated epigenetic aging are linked to long-term immune alterations in childhood cancer survivors.

    abstract:BACKGROUND:Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory di...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Daniel S,Nylander V,Ingerslev LR,Zhong L,Fabre O,Clifford B,Johnston K,Cohn RJ,Barres R,Simar D

    更新日期:2018-11-06 00:00:00

  • Genome-wide microRNA expression profiling in placentae from frozen-thawed blastocyst transfer.

    abstract:BACKGROUND:Frozen-thawed embryo transfer (FET) is increasingly available for the improvement of the success rate of assisted reproductive technologies other than fresh embryo transfer (ET). There have been numerous findings that FET provides better obstetric and perinatal outcomes. However, the birth weight of infants ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Hiura H,Hattori H,Kobayashi N,Okae H,Chiba H,Miyauchi N,Kitamura A,Kikuchi H,Yoshida H,Arima T

    更新日期:2017-08-03 00:00:00

  • High-resolution analysis of germ cells from men with sex chromosomal aneuploidies reveals normal transcriptome but impaired imprinting.

    abstract:BACKGROUND:The most common sex chromosomal aneuploidy in males is Klinefelter syndrome, which is characterized by at least one supernumerary X chromosome. While these men have long been considered infertile, focal spermatogenesis can be observed in some patients, and sperm can be surgically retrieved and used for artif...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Laurentino S,Heckmann L,Di Persio S,Li X,Meyer Zu Hörste G,Wistuba J,Cremers JF,Gromoll J,Kliesch S,Schlatt S,Neuhaus N

    更新日期:2019-08-28 00:00:00

  • Sperm imprinting integrity in seminoma patients?

    abstract:BACKGROUND:Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neopla...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Bruno C,Blagoskonov O,Barberet J,Guilleman M,Daniel S,Tournier B,Binquet C,Choux C,Fauque P

    更新日期:2018-10-19 00:00:00

  • RFX1 downregulation contributes to TLR4 overexpression in CD14+ monocytes via epigenetic mechanisms in coronary artery disease.

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    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Du P,Gao K,Cao Y,Yang S,Wang Y,Guo R,Zhao M,Jia S

    更新日期:2019-03-11 00:00:00

  • Differentially methylated loci in NAFLD cirrhosis are associated with key signaling pathways.

    abstract::Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Gerhard GS,Malenica I,Llaci L,Chu X,Petrick AT,Still CD,DiStefano JK

    更新日期:2018-07-13 00:00:00

  • Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD.

    abstract:BACKGROUND:Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) re...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Song J,Heijink IH,Kistemaker LEM,Reinders-Luinge M,Kooistra W,Noordhoek JA,Gosens R,Brandsma CA,Timens W,Hiemstra PS,Rots MG,Hylkema MN

    更新日期:2017-04-24 00:00:00

  • Erratum to: MSRE-HTPrimer: a high-throughput and genome-wide primer design pipeline optimized for epigenetic research.

    abstract::[This corrects the article DOI: 10.1186/s13148-016-0190-9.]. ...

    journal_title:Clinical epigenetics

    pub_type: 已发布勘误


    authors: Pandey RV,Pulverer W,Kallmeyer R,Beikircher G,Pabinger S,Kriegner A,Weinhäusel A

    更新日期:2016-08-04 00:00:00

  • Increased epigenetic age in normal breast tissue from luminal breast cancer patients.

    abstract:BACKGROUND:Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that o...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章,多中心研究


    authors: Hofstatter EW,Horvath S,Dalela D,Gupta P,Chagpar AB,Wali VB,Bossuyt V,Storniolo AM,Hatzis C,Patwardhan G,Von Wahlde MK,Butler M,Epstein L,Stavris K,Sturrock T,Au A,Kwei S,Pusztai L

    更新日期:2018-08-29 00:00:00

  • Overall and sex-specific associations between methylation of the ABCG1 and APOE genes and ischemic stroke or other atherosclerosis-related traits in a sibling study of Chinese population.

    abstract:BACKGROUND:Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Qin X,Li J,Wu T,Wu Y,Tang X,Gao P,Li L,Wang M,Wu Y,Wang X,Chen D,Hu Y

    更新日期:2019-12-10 00:00:00

  • Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer.

    abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Um SW,Kim HK,Kim Y,Lee BB,Kim D,Han J,Kim H,Shim YM,Kim DH

    更新日期:2017-12-20 00:00:00

  • Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking.

    abstract:BACKGROUND:Smoking is the largest preventable cause of morbidity and mortality in the United States. In previous work, we demonstrated that altered DNA methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with self-reported smoking in 19-year-old African Americans with relatively low levels of sm...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Philibert RA,Beach SR,Lei MK,Brody GH

    更新日期:2013-10-11 00:00:00

  • The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma.

    abstract::Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smok...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章,评审


    authors: Ma K,Cao B,Guo M

    更新日期:2016-04-22 00:00:00

  • DNA methylation signature of interleukin 1 receptor type II in asthma.

    abstract::Interleukin 1 and its receptors are associated with allergic diseases such as asthma. In the present study, we measured DNA methylation at the IL1R1 and IL1R2 gene loci and assessed for associations with asthma-related phenotypes and gene expressions. We found that asthmatic and atopic individuals have higher IL1R2 pr...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Gagné-Ouellet V,Guay SP,Boucher-Lafleur AM,Bouchard L,Laprise C

    更新日期:2015-08-05 00:00:00

  • Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism.

    abstract:BACKGROUND:Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD) by 44% and in diabetic CVD patients by 57% on top of statins. A phase III trial, BETonM...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Tsujikawa LM,Fu L,Das S,Halliday C,Rakai BD,Stotz SC,Sarsons CD,Gilham D,Daze E,Wasiak S,Studer D,Rinker KD,Sweeney M,Johansson JO,Wong NCW,Kulikowski E

    更新日期:2019-07-12 00:00:00

  • Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy.

    abstract:BACKGROUND:Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Jones TI,King OD,Himeda CL,Homma S,Chen JC,Beermann ML,Yan C,Emerson CP Jr,Miller JB,Wagner KR,Jones PL

    更新日期:2015-03-29 00:00:00

  • Nucleosome positioning is unaltered at MLH1 splice site mutations in cells derived from Lynch syndrome patients.

    abstract:BACKGROUND:Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Sloane MA,Hesson LB,Nunez AC,Thompson BA,Ward RL

    更新日期:2014-12-13 00:00:00

  • DNA methylation modules associate with incident cardiovascular disease and cumulative risk factor exposure.

    abstract:BACKGROUND:Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have often failed to replicate at the level o...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Westerman K,Sebastiani P,Jacques P,Liu S,DeMeo D,Ordovás JM

    更新日期:2019-10-15 00:00:00

  • Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients.

    abstract:BACKGROUND:Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Maltby VE,Graves MC,Lea RA,Benton MC,Sanders KA,Tajouri L,Scott RJ,Lechner-Scott J

    更新日期:2015-11-05 00:00:00

  • Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes.

    abstract:BACKGROUND:Inflammation has been associated with higher rates of recurrence and mortality in head and neck cancer (HNC). While the biological mechanisms predisposing patients to heightened inflammatory states remain largely unknown, DNA methylation has been proposed to reflect systemic inflammation. In this analysis, w...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Moody L,Crowder SL,Fruge AD,Locher JL,Demark-Wahnefried W,Rogers LQ,Delk-Licata A,Carroll WR,Spencer SA,Black M,Erdman JW Jr,Chen H,Pan YX,Arthur AE

    更新日期:2020-09-11 00:00:00

  • Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy.

    abstract::Duchenne muscular dystrophy (DMD) is a multisystemic disorder that affects 1:5000 boys. The severity of the phenotype varies dependent on the mutation site in the DMD gene and the resultant dystrophin expression profile. In skeletal muscle, dystrophin loss is associated with the disintegration of myofibers and their i...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章,评审


    authors: Rugowska A,Starosta A,Konieczny P

    更新日期:2021-01-19 00:00:00

  • Identification of reliable biomarkers of human papillomavirus 16 methylation in cervical lesions based on integration status using high-resolution melting analysis.

    abstract:Background:The dynamic methylation of human papillomavirus (HPV) 16 DNA is thought to be associated with the progression of cervical lesions. Previous studies that did not consider the physical status of HPV 16 may have incorrectly mapped HPV 16 methylomes. In order to identify reliable biomarkers for squamous cervical...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Liu L,Ying C,Zhao Z,Sui L,Zhang X,Qian C,Wang Q,Chen L,Guo Q,Wu J

    更新日期:2018-01-23 00:00:00