Long-term urinary adverse effects of pelvic radiotherapy

Elliott, Sean P.; Malaeb, Bahaa S.

doi:10.1007/s00345-010-0603-x

Cited by 61 publications

(50 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…25 In studies with at least 3 years of follow-up, genitourinary toxicity rates are reported from 1.3% to 14.5%. 12 Although it is difficult to compare toxicity rates of this study to others given variation in cohort and outcomes measured, toxicity rates in this study were comparable to those previously reported.…”

Section: Discussionsupporting

confidence: 62%

Treatment-Related Radiation Toxicity Among Cervical Cancer Patients

Rubinsak

Kang

Fields

et al. 2018

Int J Gynecol Cancer

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 62%

Treatment-Related Radiation Toxicity Among Cervical Cancer Patients

Rubinsak

Kang

Fields

et al. 2018

Int J Gynecol Cancer

View full text Add to dashboard Cite

show abstract

“…Although radiation effectively kills tumor cells, it also damages nearby healthy tissues. Radiotherapy for prostate cancer can cause severe long-term complications that include bowel and rectal wall damage, urinary urgency and frequency, erectile dysfunction, urethral stricture, and incontinence [3, 4]. Therefore, to improve radiation therapy-induced quality of life impairments, it is imperative to develop more effective therapies and innovative agents to protect normal tissues from radiation damage, while at the same time inhibiting tumor progression.…”

Section: Introductionmentioning

confidence: 99%

MnTE-2-PyP modulates thiol oxidation in a hydrogen peroxide-mediated manner in a human prostate cancer cell

Tong

Zhu

Galaske

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

To improve the treatment of advanced prostate cancer, the development of effective and innovative antitumor agents is needed. Our previous work demonstrated that the ROS (reactive oxygen species) scavenger, MnTE-2-PyP, inhibited human prostate cancer growth and also inhibited prostate cancer migration and invasion. We showed that MnTE-2-PyP treatment altered the affinity of the histone acetyltransferase enzyme, p300, to bind to DNA. We speculate that this may be one mechanism by which MnTE-2-PyP inhibits prostate cancer progression. Specifically, MnTE-2-PyP decreased p300/HIF-1/CREB complex (p300/hypoxia-inducible factor-1/cAMP response element-binding protein) binding to a specific hypoxia-response element (HRE) motif within the plasminogen activator inhibitor-1 (PAI-1) gene promoter region, and consequently, repressed PAI-1 expression. However, it remains unclear how MnTE-2-PyP reduces p300 complex binding affinity to the promoter region of specific genes. In this study, we found that overexpression of Cu/ZnSOD (superoxide dismutase 1, SOD1) significantly suppressed PAI-1 gene expression and p300 complex binding to the promoter region of PAI-1 gene, just as was observed in cells treated with MnTE-2-PyP. Furthermore, catalase (CAT) overexpression rescued the inhibition of PAI-1 expression and p300 binding by MnTE-2-PyP. Taken together, the above findings suggest that hydrogen peroxide (H2O2) is likely the mediator through which MnTE-2-PyP inhibits the PAI-1 expression and p300 complex binding in PC3 cells. To confirm this, we measured the production of H2O2 following overexpression of SOD1 or catalase with MnTE-2-PyP treatment in the presence or absence of radiation. We found that MnTE-2-PyP increased the intracellular steady-state levels of H2O2 and increased nuclear H2O2 levels. As expected, catalase overexpression significantly decreased the levels of intracellular H2O2 induced by MnTE-2-PyP. We then determined if this increased H2O2 production could result in oxidized protein thiol groups. In the presence of MnTE-2-PyP, there was a significant increase in oxidized thiols in PC3 cell lysates and this was reversed with catalase overexpression. Specifically, we showed that p300 was oxidized after MnTE-2-PyP treatment, indicating that MnTE-2-PyP is creating a more oxidizing environment and this is altering the oxidation state of p300 thiol residues. Our data provide an in depth mechanism by which MnTE-2-PyP regulates gene transcription through induced H2O2 mediated oxidation of particular proteins, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in prostate cancer radiotherapy.

show abstract

“…In this study, we aimed to clarify the prognostic potential of the DCE-MRI Brix model parameters in patients with cervical cancer subjected to curative chemoradiotherapy and explore Authors' Affiliations: Departments of 1 Radiation Biology, 2 Medical Physics, 3 Gynecologic Oncology; 4 Institute for Medical Informatics; their molecular background by use of gene expression profiles. In a cohort of 78 patients, we carried out pharmacokinetic analyses of pretreatment DCE-MR images and generated parameter histograms of each tumor to account for the intratumor heterogeneity in physiologic conditions.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced Gene Expression in Chemoradioresistant Cervical Cancer Revealed by Dynamic Contrast-Enhanced MRI

et al. 2012

View full text Add to dashboard Cite

Knowledge of the molecular background of functional magnetic resonance (MR) images is required to fully exploit their potential in cancer management. We explored the prognostic impact of dynamic contrastenhanced MR imaging (DCE-MRI) parameters in cervical cancer combined with global gene expression data to reveal their underlying molecular phenotype and construct a representative gene signature for the relevant parameter. On the basis of 78 patients with cervical cancer subjected to curative chemoradiotherapy, we identified the prognostic DCE-MRI parameter A Brix by pharmacokinetic analysis of pretreatment images based on the Brix model, in which tumors with low A Brix appeared to be most aggressive. Gene set analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between A Brix and the hypoxia gene sets, whereas gene sets related to other tumor phenotypes were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including both targets of the hypoxia inducible factor (HIF1a) and the unfolded protein response, were the most significant. In the remaining 32 tumors, low A Brix was associated with upregulation of HIF1a protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. On the basis of the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low A Brix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Our findings reveal the molecular basis of an aggressive hypoxic phenotype and suggest the use of DCE-MRI to noninvasively identify patients with hypoxia-related chemoradioresistance. Cancer Res; 72(20); 5285-95. Ó2012 AACR.

show abstract

Long-term urinary adverse effects of pelvic radiotherapy

Cited by 61 publications

References 55 publications

Treatment-Related Radiation Toxicity Among Cervical Cancer Patients

Treatment-Related Radiation Toxicity Among Cervical Cancer Patients

MnTE-2-PyP modulates thiol oxidation in a hydrogen peroxide-mediated manner in a human prostate cancer cell

Hypoxia-Induced Gene Expression in Chemoradioresistant Cervical Cancer Revealed by Dynamic Contrast-Enhanced MRI

Contact Info

Product

Resources

About