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  1. Article: A Systematic Review of Metabolomic and Lipidomic Candidates for Biomarkers in Radiation Injury.

    Vicente, Elisabeth / Vujaskovic, Zeljko / Jackson, Isabel L

    Metabolites

    2020  Volume 10, Issue 6

    Abstract: A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to ... ...

    Abstract A large-scale nuclear event has the ability to inflict mass casualties requiring point-of-care and laboratory-based diagnostic and prognostic biomarkers to inform victim triage and appropriate medical intervention. Extensive progress has been made to develop post-exposure point-of-care biodosimetry assays and to identify biomarkers that may be used in early phase testing to predict the course of the disease. Screening for biomarkers has recently extended to identify specific metabolomic and lipidomic responses to radiation using animal models. The objective of this review was to determine which metabolites or lipids most frequently experienced perturbations post-ionizing irradiation (IR) in preclinical studies using animal models of acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE). Upon review of approximately 65 manuscripts published in the peer-reviewed literature, the most frequently referenced metabolites showing clear changes in IR induced injury were found to be citrulline, citric acid, creatine, taurine, carnitine, xanthine, creatinine, hypoxanthine, uric acid, and threonine. Each metabolite was evaluated by specific study parameters to determine whether trends were in agreement across several studies. A select few show agreement across variable animal models, IR doses and timepoints, indicating that they may be ubiquitous and appropriate for use in diagnostic or prognostic biomarker panels.
    Language English
    Publishing date 2020-06-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo10060259
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Best Practices for Authentication of Cell Lines to Ensure Data Reproducibility and Integrity.

    Vicente, Elisabeth / Lesniewski, Megan / Newman, Diana / Vujaskovic, Zeljko / Jackson, Isabel L

    Radiation research

    2021  Volume 197, Issue 3, Page(s) 209–217

    Abstract: Cell line misidentification and contamination are major contributors to the reproducibility crisis in academic research. Authentication of cell lines provides assurances of the data generated; however, commercially available cells are often not subjected ...

    Abstract Cell line misidentification and contamination are major contributors to the reproducibility crisis in academic research. Authentication of cell lines provides assurances of the data generated; however, commercially available cells are often not subjected to rigorous identification testing. In this study, commercially available cell lines underwent testing to confirm cell identity and purity. The methods reported here outline the best practices for cell line authentication. Briefly, a commercially available primary rabbit aortic endothelial cell line was purchased for the intent of producing target proteins necessary for generating species-specific recombinant antibodies. These rabbit-specific antibodies would then be utilized for the development of in-house enzyme-linked immunosorbent assays (ELISA) to evaluate blood-based biomarkers of vascular injury after total-body irradiation. To authenticate the cell line, cell identity and purity were determined by single tandem repeat (STR) testing, flow cytometry, polymerase chain reaction (PCR), and cytochrome c oxidase subunit 1 (CO1) DNA Barcoding in-house and/or through commercial vendors. Fresh cells obtained from a New Zealand White rabbit (Charles River, Wilmington, DE) were used as a positive control. The results of STR and flow cytometry analyses indicated the cells were not contaminated with human or mouse cells, and that the cells were not of endothelial origin. PCR demonstrated that cells were also not of rabbit origin, which was further confirmed by a third-party vendor. An unopened vial of cells was submitted to another vendor for CO1 DNA Barcoding analysis, which identified the cells as being purely of bovine origin. Results revealed that despite purchase through a commercial vendor, the cell line marketed as primary rabbit aortic endothelial cells were of bovine origin. Purity analysis found cells were misidentified rather than contaminated. Further investigation to determine the cell type was not performed. The most cost-effective and efficient methodology for confirming cell line identity was found to be CO1 DNA Barcoding performed by a commercial vendor.
    MeSH term(s) Animals ; Cattle ; Cell Line ; DNA ; Endothelial Cells ; Mice ; Polymerase Chain Reaction ; Rabbits ; Reproducibility of Results
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2021-12-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80322-4
    ISSN 1938-5404 ; 0033-7587
    ISSN (online) 1938-5404
    ISSN 0033-7587
    DOI 10.1667/RADE-21-00148.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Radiosensitization of high-grade gliomas through induced hyperthermia: Review of clinical experience and the potential role of MR-guided focused ultrasound.

    Schneider, Craig S / Woodworth, Graeme F / Vujaskovic, Zeljko / Mishra, Mark V

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

    2019  Volume 142, Page(s) 43–51

    Abstract: High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies ...

    Abstract High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies for HGGs; however, standard treatments have not changed significantly in more than 10 years, since the introduction of concurrent chemoradiation therapy with temozolomide. Hyperthermia (HT) has been shown to enhance the efficacy of radiation treatment (RT) in numerous cancer types through multiple mechanisms, including impairment of DNA repair pathways, increased perfusion/oxygenation of tumors, and immune system activation. In the 1980s and 1990s, the combination of HT with external-beam RT and interstitial brachytherapy was extensively evaluated in HGG, culminating in a randomized controlled trial that demonstrated superior survival in patients receiving combined HT and RT. However, HT was not adopted into common practice for HGG because of the need at that time for invasive implantation procedures, challenges to monitoring and maintaining a homogeneous, localized temperature elevation within the tumor tissue, as well as other technical and logistic challenges. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a relatively new technology in clinical use that is capable of highly accurate transcranial HT and has the potential to overcome many of the limitations faced in previous trials combining HT and RT in HGG. In this review, we detail and compile the previous clinical results of combined HT and RT in HGG patients. We also introduce and discuss the potential of MRgFUS as a noninvasive method for HT to radiosensitize HGG.
    MeSH term(s) Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Brain Neoplasms/therapy ; Combined Modality Therapy ; Glioma/diagnostic imaging ; Glioma/pathology ; Glioma/radiotherapy ; Glioma/therapy ; Humans ; Hyperthermia, Induced/methods ; Magnetic Resonance Imaging/methods ; Neoplasm Recurrence, Local/diagnostic imaging ; Neoplasm Recurrence, Local/radiotherapy ; Neoplasm Recurrence, Local/therapy ; Randomized Controlled Trials as Topic ; Ultrasonography/methods
    Language English
    Publishing date 2019-08-17
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 605646-5
    ISSN 1879-0887 ; 0167-8140
    ISSN (online) 1879-0887
    ISSN 0167-8140
    DOI 10.1016/j.radonc.2019.07.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Impact of bowel and rectum air on target dose with robustly optimized intensity-modulated proton therapy plans.

    Yao, Weiguang / Schweitzer, Noah / Biswal, Nrusingh / Polf, Jerimy / Farr, Jonathan / Vujaskovic, Zeljko

    Acta oncologica (Stockholm, Sweden)

    2020  Volume 59, Issue 10, Page(s) 1186–1192

    Abstract: Purpose: Pelvic target dose from intensity-modulated proton therapy (IMPT) is sensitive to patient bowel motion. Robustly optimized plans in regard to bowel filling may improve the dose coverage in the treatment course. Our purpose is to investigate the ...

    Abstract Purpose: Pelvic target dose from intensity-modulated proton therapy (IMPT) is sensitive to patient bowel motion. Robustly optimized plans in regard to bowel filling may improve the dose coverage in the treatment course. Our purpose is to investigate the effect of air volume in large and small bowel and rectum on target dose from IMPT plans.
    Methods and material: Data from 17 cancer patients (11 prostate, 3 gynecologic, 2 colon, and 1 embryonal rhabdomyosarcoma) with planning CT (pCT) and weekly or biweekly scanned quality assurance CTs (QACTs; 82 QACT scans total) were studied. Air in bowels and rectum traversed by proton pencil beams was contoured. The robust treatment plan was made by using 3 CT sets: the pCT set and 2 virtual CT sets that were copies of pCT but in which the fillings of bowels and rectum were overridden to be either air or muscle. Each plan had 2-5 beams with a mean of 3 beams. Targets in the pCT were mapped to the QACTs by deformable image registration, and the dose in QACTs was calculated. Dose coverage (D99 and D95) and correlations between dose coverage and changes in air volume were analyzed. The significance of the correlation was analyzed by
    Results: Mean changes of D99 in QACTs were within 3% of those in the pCT for all prostate and colon cases but >3% in 2 of the 3 gynecologic cases and in the embryonal rhabdomyosarcoma case. Of these three cases with mean change of D99 > 3%, air volume may be the main cause in 2. For the prostate cases, correlation coefficients were <0.7 between change in air volume and change in D99 and D95, because other anatomy changes also contributed to dose deviation. Correlation coefficients in the non-prostate cases were >0.9 between D99 change and rectum and between D95 change and small bowel, indicating a greater effect of the air volume on target dose.
    Conclusion: The air volume may still have an important effect on target dose coverage in treatment plans using 3 CT sets, particularly when the air is traversed by multiple beams.
    MeSH term(s) Air ; Humans ; Intestine, Large/physiopathology ; Neoplasms/radiotherapy ; Organs at Risk ; Proton Therapy ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; Rectum/physiopathology
    Language English
    Publishing date 2020-06-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 896449-x
    ISSN 1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
    ISSN (online) 1651-226X
    ISSN 0349-652X ; 0284-186X ; 1100-1704
    DOI 10.1080/0284186X.2020.1769859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Use of CT simulation and 3-D radiation therapy treatment planning system to develop and validate a total-body irradiation technique for the New Zealand White rabbit.

    Poirier, Yannick / Prado, Charlotte / Prado, Karl / Draeger, Emily / Jackson, Isabel L / Vujaskovic, Zeljko

    International journal of radiation biology

    2020  Volume 97, Issue sup1, Page(s) S10–S18

    Abstract: Purpose: Well-controlled ionizing radiation injury animal models for testing medical countermeasure efficacy require robust radiation physics and dosimetry to ensure accuracy of dose-delivery and reproducibility of the radiation dose-response ... ...

    Abstract Purpose: Well-controlled ionizing radiation injury animal models for testing medical countermeasure efficacy require robust radiation physics and dosimetry to ensure accuracy of dose-delivery and reproducibility of the radiation dose-response relationship. The objective of this study was to establish a simple, convenient, robust and accurate technique for validating total body irradiation (TBI) exposure of the New Zealand White rabbit.
    Methods: We use radiotherapy techniques such as computed tomography simulation and a 3 D-conformal radiation therapy treatment planning system (TPS) on three animals to comprehensively design and preplan a TBI technique for rabbits. We evaluate the requirement for bolus, treatment geometry, bilateral vs anterior-posterior treatment delivery, the agreement between monitor units calculated using the TPS vs a traditional hand calculation to the mid-plane, and resulting individual organ doses.
    Results: The optimal technique irradiates animals on the left-decubitus position using two isocentric bilateral parallel-opposed 6 MV x-ray beams. Placement of a 5 mm bolus and 8.5 mm beam spoiler was shown to increase the dose to within ≤5 mm of the surface, improving dose homogeneity throughout the body of the rabbit. A simple hand calculation formalism, dependent only on mid-abdominal separation, could be used to calculate the number of monitor units (MUs) required to accurately deliver the prescribed dose to the animal. For the representative animal, the total body volume receiving > 95% of the dose, V
    Conclusion: The TBI technique developed in this pilot study was successfully used to establish the dose-response relationship for 45-day lethality across the dose-range to induce the hematopoietic-subsyndrome of the acute radiation syndrome (ARS).
    MeSH term(s) Animals ; Phantoms, Imaging ; Pilot Projects ; Rabbits ; Radiometry/methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Reproducibility of Results ; Tomography, X-Ray Computed ; Whole-Body Irradiation
    Language English
    Publishing date 2020-09-24
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 3065-x
    ISSN 1362-3095 ; 0020-7616 ; 0955-3002
    ISSN (online) 1362-3095
    ISSN 0020-7616 ; 0955-3002
    DOI 10.1080/09553002.2019.1665215
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients With Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy.

    Simone, Charles B / Serebrenik, Artur A / Gore, Elizabeth M / Mohindra, Pranshu / Brown, Stephen L / Wang, Ding / Chetty, Indrin J / Vujaskovic, Zeljko / Menon, Smitha / Thompson, Jonathan / Fine, Gil / Kaytor, Michael D / Movsas, Benjamin

    International journal of radiation oncology, biology, physics

    2023  Volume 118, Issue 2, Page(s) 404–414

    Abstract: Purpose: Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These ... ...

    Abstract Purpose: Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination and worsening clinical outcomes in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC.
    Methods and materials: In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60 to 70/1.8-2.0 Gy radiation therapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/d; cohort 2, 1000 mg/d; cohort 3, 1500 mg/d) was self-administered once daily starting 2 to 7 days before initiating concurrent chemoradiotherapy and continued until the end of radiation therapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival.
    Results: Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (n = 11) were all mild to moderate in severity (grade 1, n = 9; grade 2, n = 2) and predominantly gastrointestinal (n = 7). A dose-dependent decrease in serum transforming growth factor β1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient-reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate).
    Conclusions: The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemoradiotherapy/adverse effects ; Chemoradiotherapy/methods ; Carboplatin ; Paclitaxel
    Chemical Substances Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2023-08-29
    Publishing country United States
    Document type Multicenter Study ; Clinical Trial, Phase I ; Journal Article
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2023.08.048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Hyperthermia and radiotherapy in bladder cancer.

    Snider, James William / Datta, Niloy Ranjan / Vujaskovic, Zeljko

    International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

    2016  Volume 32, Issue 4, Page(s) 398–406

    Abstract: Hyperthermia represents a unique, safe, and advantageous methodology for improving therapeutic strategies in the management of bladder cancer. This modality has shown promise in contributing to treatment regimens for both superficial and muscle-invasive ... ...

    Abstract Hyperthermia represents a unique, safe, and advantageous methodology for improving therapeutic strategies in the management of bladder cancer. This modality has shown promise in contributing to treatment regimens for both superficial and muscle-invasive disease. Especially in conjunction with intravesical chemotherapy, systemic therapy, and radiotherapy, hyperthermia shows particular synergistic benefit. As such, it should be explored further through clinical use and clinical trial in conjunction with currently available techniques and emerging technologies. However, to conceptualise the way forward, it is particularly important to understand the current challenges to widespread use of non-invasive, bladder-sparing approaches and the current state of bladder cancer care. As such, in the following article, we have focused on not only the rationale for concurrent radiotherapy and hyperthermia, but also the clinical landscape in bladder cancer as a whole.
    Language English
    Publishing date 2016-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 632526-9
    ISSN 1464-5157 ; 0265-6736
    ISSN (online) 1464-5157
    ISSN 0265-6736
    DOI 10.3109/02656736.2016.1150524
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction: Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

    Leiser, Dominic / Samanta, Santanu / Strauss, Josh / Eley, John / Creed, Michael / Kingsbury, Tami / Staats, Paul N / Bhandary, Binny / Chen, Minjie / Dukic, Tijana / Roy, Sanjit / Mahmood, Javed / Vujaskovic, Zeljko / Shukla, Hem D

    PloS one

    2022  Volume 17, Issue 5, Page(s) e0268256

    Abstract: This corrects the article DOI: 10.1371/journal.pone.0258951.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pone.0258951.].
    Language English
    Publishing date 2022-05-03
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0268256
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  9. Article ; Online: Interspecies Comparison and Radiation Effect on Pharmacokinetics of BIO 300, a Nanosuspension of Genistein, after Different Routes of Administration in Mice and Non-Human Primates.

    Salem, Ahmed M / Jackson, Isabel L / Gibbs, Allison / Poirier, Yannick / Newman, Diana / Zodda, Andrew / Vujaskovic, Zeljko / Kaytor, Michael D / Serebrenik, Artur A / Gobburu, Jogarao / Gopalakrishnan, Mathangi

    Radiation research

    2022  Volume 197, Issue 5, Page(s) 447–458

    Abstract: BIO 300, a suspension of synthetic genistein nanoparticles, is being developed for mitigating the delayed effects of acute radiation exposure (DEARE). The purpose of the current study was to characterize the pharmacokinetic (PK) profile of BIO 300 ... ...

    Abstract BIO 300, a suspension of synthetic genistein nanoparticles, is being developed for mitigating the delayed effects of acute radiation exposure (DEARE). The purpose of the current study was to characterize the pharmacokinetic (PK) profile of BIO 300 administered as an oral or parenteral formulation 24 h after sham-irradiation, total-body irradiation (TBI) with 2.5-5.0% bone marrow sparing (TBI/BMx), or in nonirradiated sex-matched C57BL/6J mice and non-human primates (NHP). C57BL/6J mice were randomized to the following arms in two consecutive studies: sham-TBI [400 mg/kg, oral gavage (OG)], TBI/BM2.5 (400 mg/kg, OG), sham-TBI [200 mg/kg, subcutaneous (SC) injection], TBI/BM2.5 (200 mg/kg, SC), sham-TBI (100 mg/kg, SC), or nonirradiated [200 mg/kg, intramuscular (IM) injection]. The PK profile was also established in NHP exposed to TBI/BM5.0 (100 mg/kg, BID, OG). Genistein-aglycone serum concentrations were measured in all groups using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The PK profile demonstrates 11% and 19% reductions in Cmax and AUC0-inf, respectively, among mice administered 400 mg/kg, OG, after TBI/BM2.5 compared to the sham-TBI control arm. Administration of 200 mg/kg SC in mice exposed to TBI/BM2.5 showed a 53% increase in AUC0-inf but a 28% reduction in Cmax compared to the sham-TBI mice. The relative bioavailability of the OG route compared to the SC and IM routes in mice was 9% and 7%, respectively. After the OG route, the dose-normalized AUC0-inf was 13.37 (ng.h/mL)/(mg/kg) in TBI/BM2.5 mice compared to 6.95 (ng.h/mL)/(mg/kg) in TBI/BM5.0 NHPs. Linear regression of apparent clearances and weights of mice and NHPs yielded an allometric coefficient of 1.06. Based on these data, the effect of TBI/BMx on BIO 300 PK is considered minimal. Future studies should use SC and IM routes to maximize drug exposure when administered postirradiation. The allometric coefficient is useful in predicting therapeutic drug dose regimens across species for drug approval under the FDA animal rule.
    MeSH term(s) Animals ; Chromatography, Liquid ; Genistein ; Mice ; Mice, Inbred C57BL ; Primates ; Tandem Mass Spectrometry
    Chemical Substances Genistein (DH2M523P0H)
    Language English
    Publishing date 2022-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80322-4
    ISSN 1938-5404 ; 0033-7587
    ISSN (online) 1938-5404
    ISSN 0033-7587
    DOI 10.1667/RADE-21-00114.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Integrated proteo-genomic approach for early diagnosis and prognosis of cancer.

    Shukla, Hem D / Mahmood, Javed / Vujaskovic, Zeljko

    Cancer letters

    2015  Volume 369, Issue 1, Page(s) 28–36

    Abstract: Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and ... ...

    Abstract Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair. These somatic DNA mutations known as driver mutations seem to be the prime cause in initiating tumorigenesis. The advances in genomic technologies have immensely facilitated the understanding of cancer progression and metastasis, and the discovery of novel biomarkers. However, changes in somatic mutational landscape of the oncogenome are translated into aberrantly regulated oncoproteome which drives the cancer initiation. Thus, combination of proteomic and genomic technologies is urgently required to discover biomarkers for early diagnosis. The recent advances in human genome based detection of cancer using advanced genomic technologies like NextGen Sequencing, digital PCR, cfDNA technology have shown promise; for example oncogenic somatic mutation variants, transcriptomic analysis, copy number variant, and methylation data from the Cancer Genome Atlas. Similarly, oncoproteomics has the potential to revolutionize clinical management of the disease, including cancer diagnosis and screening based on new proteomic database which embodies somatic variants and post translational modifications, thus devising proteomic technologies as a complement to histopathology. Further, the use of multiple proteomic and genomic biomarkers rather than a single gene or protein could greatly improve diagnostic accuracy and enhance the predictive power for treatment outcome and may enable adequate monitoring of the response to treatment and could be an important option for personalized medicine. The proteogenomic approach has the promise to identify new biomarkers for radiation therapy (RT) which could reliably predict the tumor radiation resistance and which could also accurately predict normal tissue toxicity, and at the same time radiotherapy effectiveness. In this review we have summarize the recent advances in proteogenomic approaches to develop more sensitive diagnostic and prognostic biomarkers which could be translated into improved clinical care and management of the disease.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Early Detection of Cancer ; Humans ; Neoplasms/diagnosis ; Neoplasms/metabolism ; Neoplasms/radiotherapy ; Precision Medicine ; Prognosis ; Proteome/metabolism ; Proteomics ; Radiation Tolerance
    Chemical Substances Biomarkers, Tumor ; Proteome
    Language English
    Publishing date 2015-12-01
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2015.08.003
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