DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice
Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for dissemina...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4186 |
| _version_ | 1797524363872829440 |
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| author | Palak R. Parekh Eduardo Solano-Gonzalez Mariana B. Martins Xinrong Ma Kayla Tighe Andrea Casildo Andrew Zodda Christopher Johnstone Yannick Poirier Javed Mahmood Kavita Bhalla Sheri Li Rena G. Lapidus France Carrier |
| author_facet | Palak R. Parekh Eduardo Solano-Gonzalez Mariana B. Martins Xinrong Ma Kayla Tighe Andrea Casildo Andrew Zodda Christopher Johnstone Yannick Poirier Javed Mahmood Kavita Bhalla Sheri Li Rena G. Lapidus France Carrier |
| author_sort | Palak R. Parekh |
| collection | DOAJ |
| description | Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, Dual Oxidase 2 (DUOX2). Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or reduced levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; modified regimen of docetaxel, cisplatin and 5′-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 0.15 Gy in three days), 4; mDCF and LD-WART. The combined regimen increased the odds of preventing cancer dissemination (mDCF + LD-WART OR = 4.16; 80% CI = 1.0, 17.29) in the DUOX2 positive tumors, while tumors expressing lower DUOX2 levels were more responsive to mDCF alone with no added benefit from LD-WART. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-κB upregulation. These data are particularly important since our study indicates that about 33% of human stomach adenocarcinoma do not express DUOX2. DUOX2 thus seems a likely biomarker for potential clinical application of chemopotentiation by LD-WART. |
| first_indexed | 2024-03-10T08:56:18Z |
| format | Article |
| id | doaj.art-31eea971bed24792b9d5956ffcaa8976 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:56:18Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-31eea971bed24792b9d5956ffcaa89762023-11-22T07:05:05ZengMDPI AGCancers2072-66942021-08-011316418610.3390/cancers13164186DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in MicePalak R. Parekh0Eduardo Solano-Gonzalez1Mariana B. Martins2Xinrong Ma3Kayla Tighe4Andrea Casildo5Andrew Zodda6Christopher Johnstone7Yannick Poirier8Javed Mahmood9Kavita Bhalla10Sheri Li11Rena G. Lapidus12France Carrier13Veterans Affairs Maryland Health Care System, Baltimore, MD 21201, USAVeterans Affairs Maryland Health Care System, Baltimore, MD 21201, USADivision of Translational Radiation Sciences, Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USATranslational Laboratory Shared Services, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USATranslational Laboratory Shared Services, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USATranslational Laboratory Shared Services, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USADivision of Translational Radiation Sciences, Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USADivision of Translational Radiation Sciences, Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USADivision of Translational Radiation Sciences, Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USAVeterans Affairs Maryland Health Care System, Baltimore, MD 21201, USAVeterans Affairs Maryland Health Care System, Baltimore, MD 21201, USADivision of Translational Radiation Sciences, Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, MD 21201, USATranslational Laboratory Shared Services, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USAVeterans Affairs Maryland Health Care System, Baltimore, MD 21201, USATreatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, Dual Oxidase 2 (DUOX2). Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or reduced levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; modified regimen of docetaxel, cisplatin and 5′-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 0.15 Gy in three days), 4; mDCF and LD-WART. The combined regimen increased the odds of preventing cancer dissemination (mDCF + LD-WART OR = 4.16; 80% CI = 1.0, 17.29) in the DUOX2 positive tumors, while tumors expressing lower DUOX2 levels were more responsive to mDCF alone with no added benefit from LD-WART. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-κB upregulation. These data are particularly important since our study indicates that about 33% of human stomach adenocarcinoma do not express DUOX2. DUOX2 thus seems a likely biomarker for potential clinical application of chemopotentiation by LD-WART.https://www.mdpi.com/2072-6694/13/16/4186gastric cancerlow dose radiation therapyDual oxidase 2 |
| spellingShingle | Palak R. Parekh Eduardo Solano-Gonzalez Mariana B. Martins Xinrong Ma Kayla Tighe Andrea Casildo Andrew Zodda Christopher Johnstone Yannick Poirier Javed Mahmood Kavita Bhalla Sheri Li Rena G. Lapidus France Carrier DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice Cancers gastric cancer low dose radiation therapy Dual oxidase 2 |
| title | DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice |
| title_full | DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice |
| title_fullStr | DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice |
| title_full_unstemmed | DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice |
| title_short | DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice |
| title_sort | duox2 a new biomarker for disseminated gastric cancer s response to low dose radiation in mice |
| topic | gastric cancer low dose radiation therapy Dual oxidase 2 |
| url | https://www.mdpi.com/2072-6694/13/16/4186 |
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