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Project Title:  Determining Gender Differences in the Incidence of Lung Adenocarcinoma After Space Radiation Exposure Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 09/01/2018  
End Date: 08/31/2024  
Task Last Updated: 11/07/2023 
Download report in PDF pdf
Principal Investigator/Affiliation:   Story, Michael D Ph.D. / University of Texas, Southwestern Medical Center 
Address:  Division of Molecular Radiation Biology 
2201 Inwood Rd., Room NC7.206 
Dallas , TX 75235-7320 
Email: michael.story@utsouthwestern.edu 
Phone: 214 648 5557  
Congressional District: 30 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Texas, Southwestern Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lianghao, Ding  Ph.D. University of Texas Southwestern Medical Center, Dallas 
Project Information: Grant/Contract No. 80NSSC18K1676 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12048 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC18K1676 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
Human Research Program Gaps: (1) Cancer-103:Determine the effects of radiation quality on cancer initiation, promotion, and progression.
(2) Cancer-203:Evaluate the tissue-specific risks of space radiation exposure on cancer outcomes.
(3) Cancer-204:Evaluate the sex-specific risks of space radiation exposure on cancer outcomes.
(4) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
Flight Assignment/Project Notes: NOTE: End date changed to 08/31/2024 per JSC Grants Office and NSSC information (Ed., 4/11/23)

Task Description: Uncertainties in radiation induced lung cancer risk estimation and its associated mortality rates are among the primary factors limiting the number of safe days an astronaut can spend in space. Initial lung cancer risks are based off epidemiological-based modeling and include cohorts such as the atomic bomb survivor life span study (LSS) whose estimates contain large confidence intervals and whose populations may not reflect astronauts on deep space missions. In order to calculate the permissible exposure limit (PEL) for astronauts it is necessary to collect further information on the risk of lung carcinogenesis due to radiation quality differences (relative biological effectiveness--RBE), sex disparities, and how effective biological countermeasures may reduce or mitigate these risks.

The goal of this project is to provide sufficient data to bolster risk estimates and RBE values for lung carcinogenesis from the individual small, intermediate, and heavy charged particles that comprise galactic cosmic rays (GCRs) with doses comparable to what an astronaut may receive on a Mars mission. Additionally we will delineate any sex differences in radiogenic lung cancer risk resulting from space radiation exposure, provide sufficient evidence to validate GC4419, a Food & Drug Administration (FDA investigational new drug (IND), as an effective pharmaceutical countermeasure, and mechanistically define the biological processes associated with space radiation induced lung carcinogenesis.

Research Impact/Earth Benefits: There are two areas where this research may benefit life on Earth.

1) Differences in both the incidence of and mortality arising from lung cancer between men and women have long been appreciated, with women generally having higher incidences and mortality rates than men. Epidemiological studies comparing pre- and post-menopausal women treated with hormone replacement therapy (HRT) have demonstrated that female sex hormones both elevated the incidence and aggressiveness at the time of presentation. These effects likely enhance the efficacy of other carcinogens such as radiation or tobacco smoke.

2) GC4419 is a radioprotector for radiation-induced mucositis and lung fibrosis from radiation exposure. What is not known, although the preliminary evidence suggests it could, is whether GC4419 has anti-carcinogenic effects. If it does, the potential to reduce the risk for cancer in humans after environmental or diagnostic radiation exposures is compelling.

Task Progress & Bibliography Information FY2023 
Task Progress: For all Aims, 4,565 animals have been irradiated or served as controls. 3,975 animals have completed the study. There are still 2 cohorts of animals under study those being the avasopasem treated unirradiated animals and the cohort irradiated with 1.5 Gy 137Cs and treated with avasopasem for a total of 483 mice remaining. 556 suspected lung tumors have been collected and roughly 240 have been sent to pathology for processing. 160 are ready for pathologic analysis to confirm and describe lung tumors in a blinded fashion. Interestingly, other non-cancer pathologies have been identified including hematologic ovarian cysts and tumors, and hepatosplenomegaly. Interestingly, survival of the 1.5 Gy 137Cs-irradiated cohort treated with avasopasem is higher than the cohort not treated with avasopasem although the p-value at this point is ~0.06. This avasopasem-treated cohort will continue until the termination point. The avasopasem-treated unirradiated cohort will continue for another approximately 6 months.

Constraints: While lung tissue, lung masses and tumor.

Oral Presentations: 2023 NASA Human Research Program Investigators' Workshop (IWS), Galveston, Texas, February 7-9, 2023. Oral presentation by Sorour Hosseini. Is lung cancer risk after space radiation exposure higher in females than in males, and can SOD mimetic GC4419 act as a radiation countermeasure? S. Hosseini, Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.

Hosseini S, Sishc BJ, Ramnarain D, Polsdofer EM, Story MD. 2023 American Association of Physicists in Medicine (AAPM) 65th Annual Meeting Houston, Texas. July 23-27, 2023. Oral presentation by Sorour Hosseini. Avasopasem manganese protects and mitigates radiation-induced lung fibrosis, reduces radiogenic lung cancers and extends survival in mice irradiated with either low LET or high LET radiations simulating the space environment.

Poster Presentations: Hosseini S, Polsdofer EM, Felix D, Nicholson J, Ding L-H, Wight-Carter M, Story MD. 2023 International Congress on Radiation Research (ICRR), Montreal, Canada, August 26-30, 2023. Poster presentation, Michael Story. Evaluating the potential of the SOD mimetic Avasopasem Manganese as a radiation countermeasure for space radiation-induced lung cancer.

Bibliography: Description: (Last Updated: 12/14/2023) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Hosseini S, Sishc BJ, Ramnarain D, Polsdofer EM, Story MD. "Avasopasem manganese protects and mitigates radiation-induced lung fibrosis, reduces radiogenic lung cancers and extends survival in mice irradiated with either low LET or high LET radiations simulating the space environment." AAPM 2023. 65th Annual Meeting and Exhibition of the American Association of Physicists in Medicine, Houston, Texas, July 23-27, 2023.

Abstracts. AAPM 2023. 65th Annual Meeting and Exhibition of the American Association of Physicists in Medicine, Houston, Texas, July 23-27, 2023. , Jul-2023

Project Title:  Determining Gender Differences in the Incidence of Lung Adenocarcinoma After Space Radiation Exposure Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 09/01/2018  
End Date: 08/31/2024  
Task Last Updated: 07/05/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Story, Michael D Ph.D. / University of Texas, Southwestern Medical Center 
Address:  Division of Molecular Radiation Biology 
2201 Inwood Rd., Room NC7.206 
Dallas , TX 75235-7320 
Email: michael.story@utsouthwestern.edu 
Phone: 214 648 5557  
Congressional District: 30 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Texas, Southwestern Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lianghao, Ding  Ph.D. University of Texas Southwestern Medical Center, Dallas 
Project Information: Grant/Contract No. 80NSSC18K1676 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12048 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC18K1676 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
Human Research Program Gaps: (1) Cancer-103:Determine the effects of radiation quality on cancer initiation, promotion, and progression.
(2) Cancer-203:Evaluate the tissue-specific risks of space radiation exposure on cancer outcomes.
(3) Cancer-204:Evaluate the sex-specific risks of space radiation exposure on cancer outcomes.
(4) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
Flight Assignment/Project Notes: NOTE: End date changed to 08/31/2024 per JSC Grants Office and NSSC information (Ed., 4/11/23)

Task Description: Uncertainties in radiation induced lung cancer risk estimation and its associated mortality rates are among the primary factors limiting the number of safe days an astronaut can spend in space. Initial lung cancer risks are based off epidemiological-based modeling and include cohorts such as the atomic bomb survivor life span study (LSS) whose estimates contain large confidence intervals and whose populations may not reflect astronauts on deep space missions. In order to calculate the permissible exposure limit (PEL) for astronauts it is necessary to collect further information on the risk of lung carcinogenesis due to radiation quality differences (relative biological effectiveness--RBE), sex disparities, and how effective biological countermeasures may reduce or mitigate these risks.

The goal of this project is to provide sufficient data to bolster risk estimates and RBE values for lung carcinogenesis from the individual small, intermediate, and heavy charged particles that comprise galactic cosmic rays (GCRs) with doses comparable to what an astronaut may receive on a Mars mission. Additionally we will delineate any sex differences in radiogenic lung cancer risk resulting from space radiation exposure, provide sufficient evidence to validate GC4419, a Food & Drug Administration (FDA investigational new drug (IND), as an effective pharmaceutical countermeasure, and mechanistically define the biological processes associated with space radiation induced lung carcinogenesis.

Research Impact/Earth Benefits: There are two areas where this research may benefit life on Earth.

1) Differences in both the incidence of and mortality arising from lung cancer between men and women have long been appreciated, with women generally having higher incidences and mortality rates than men. Epidemiological studies comparing pre- and post-menopausal women treated with hormone replacement therapy (HRT) have demonstrated that female sex hormones both elevated the incidence and aggressiveness at the time of presentation. These effects likely enhance the efficacy of other carcinogens such as radiation or tobacco smoke. We are following the production of estrogen for 8 weeks post-IR (irradiation) to determine whether space radiation is more effective at reducing estrogen via the radioresponse of the mouse ovary. We will follow lung cancer in mice with lower estrogen to determine the impact on ovarian function and risk for radiation-induced lung cancer. We may also consider estrogen replacement to determine how "hormone replacement" alters lung cancer risk from radiation exposure.

2) GC4419 is a radioprotector for radiation-induced mucositis and lung fibrosis from radiation exposure. What is not known, although the preliminary evidence suggests it could, is whether GC4419 has anti-carcinogenic effects. If it does, the potential to reduce the risk for cancer in humans after environmental or diagnostic radiation exposures is compelling.

Task Progress & Bibliography Information FY2022 
Task Progress: After more than a year of delays due to the COVID-19 pandemic, we have successfully carried out radiation experiments using the Galactic Cosmic Radiation simulation beam (GCRsim) during the NASA Space Radiation Laboratory (NSRL) runs of Spring and Summer 2021. In addition, we have completed our gamma irradiations with the putative countermeasure GC4419. As it stands, 19 out of 19 cohorts, including all planned irradiations, GC4419 injections and control groups, are in progress. A total of 4685 mice were enrolled in this project and 636 lung masses have been collected pending pathological examinations at this point. The number of lung masses is expected to increase because the radioprotector cohorts are still at an early stage. The consequence of delayed GCRsim and both gamma and GCRsim experiments will push the completion of countermeasure study into a putative year 6. In addition to the isolation of lung masses, we have also been collecting tissue and plasma for molecular analysis for our biomarker studies. A similar study was carried out for radiation induced hepatocellular carcinoma with the identification of 4 miRNA as sentinels for hepatocellular carcinoma development. We have performed radiation survival analysis using mouse survival data collected so far. The preliminary results suggested that differences between sex may exist in the risk of radiation-related death, albeit the data need statistical analysis. Also in preliminary findings, the mouse cohort administered with GC4419 and irradiated with the GCRsim beams appeared to be separated from the cohort without GC4419, and to be more radioresistant in terms of survival, that is, acting as a radiation countermeasure. Whether that includes a reduction in radiation-induced cancers will not be known for some time.

Bibliography: Description: (Last Updated: 12/14/2023) 

Show Cumulative Bibliography
 
 None in FY 2022
Project Title:  Determining Gender Differences in the Incidence of Lung Adenocarcinoma After Space Radiation Exposure Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 09/01/2018  
End Date: 08/31/2022  
Task Last Updated: 06/30/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Story, Michael D Ph.D. / University of Texas, Southwestern Medical Center 
Address:  Division of Molecular Radiation Biology 
2201 Inwood Rd., Room NC7.206 
Dallas , TX 75235-7320 
Email: michael.story@utsouthwestern.edu 
Phone: 214 648 5557  
Congressional District: 30 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Texas, Southwestern Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lianghao, Ding  Ph.D. University of Texas Southwestern Medical Center, Dallas 
Project Information: Grant/Contract No. 80NSSC18K1676 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Unique ID: 12048 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC18K1676 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
Human Research Program Gaps: (1) Cancer-103:Determine the effects of radiation quality on cancer initiation, promotion, and progression.
(2) Cancer-203:Evaluate the tissue-specific risks of space radiation exposure on cancer outcomes.
(3) Cancer-204:Evaluate the sex-specific risks of space radiation exposure on cancer outcomes.
(4) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
Task Description: Uncertainties in radiation induced lung cancer risk estimation and its associated mortality rates are among the primary factors limiting the number of safe days an astronaut can spend in space. Initial lung cancer risks are based off epidemiological-based modeling and include cohorts such as the atomic bomb survivor life span study (LSS) whose estimates contain large confidence intervals and whose populations may not reflect astronauts on deep space missions. In order to calculate the permissible exposure limit (PEL) for astronauts it is necessary to collect further information on the risk of lung carcinogenesis due to radiation quality differences (relative biological effectiveness--RBE), sex disparities, and how effective biological countermeasures may reduce or mitigate these risks.

The goal of this project is to provide sufficient data to bolster risk estimates and RBE values for lung carcinogenesis from the individual small, intermediate, and heavy charged particles that comprise galactic cosmic rays (GCRs) with doses comparable to what an astronaut may receive on a Mars mission. Additionally we will delineate any sex differences in radiogenic lung cancer risk resulting from space radiation exposure, provide sufficient evidence to validate GC4419, a Food & Drug Administration (FDA investigational new drug (IND), as an effective pharmaceutical countermeasure, and mechanistically define the biological processes associated with space radiation induced lung carcinogenesis.

Research Impact/Earth Benefits: There are two areas where this research may benefit life on Earth.

1) Differences in both the incidence of and mortality arising from lung cancer between men and women have long been appreciated, with women generally having higher incidences and mortality rates than men. Epidemiological studies comparing pre- and post-menopausal women treated with hormone replacement therapy (HRT) have demonstrated that female sex hormones both elevated the incidence and aggressiveness at the time of presentation. These effects likely enhance the efficacy of other carcinogens such as radiation or tobacco smoke. We are following the production of estrogen for 8 weeks post-IR (irradiation) to determine whether space radiation is more effective at reducing estrogen via the radioresponse of the mouse ovary. We will follow lung cancer in mice with lower estrogen to determine the impact on ovarian function and risk for radiation-induced lung cancer. We may also consider estrogen replacement to determine how "hormone replacement" alters lung cancer risk from radiation exposure.

2) GC4419 is a radioprotector for radiation-induced mucositis and lung fibrosis from radiation exposure. What is not known, although the preliminary evidence suggests it could, is whether GC4419 has anti-carcinogenic effects. If it does, the potential to reduce the risk for cancer in humans after environmental or diagnostic radiation exposures is compelling.

Task Progress & Bibliography Information FY2020 
Task Progress: In pursuit of the aims of this project we will sample normal lung tissue, plasma, and tumors from irradiated or not cohorts of BALB/c mice. These tissue samples will be subject to histologic, gene, and miRNA expression, the presence of circulating miRNA, and copy number variation analysis in the context of sex differences as well to determine if there is a bio-signature indicative of sex differences. Immune histochemistry for estrogen signaling will be carried out to confirm gene or miRNA expression data associated with hormonal signaling.

To date we have carried out irradiations in 13 of 21 cohorts. We have now irradiated our gamma-ray cohorts at 0.4, 0.75, and 1.5 Gy (females) and our 0.75 Gy cohort of male mice, or Si irradiations at 0.1, 0.2, and 0.4 Gy (male and female) and our Galactic Cosmic Radiation simulation beam (GCRsim) at 0.2 and 0.75 Gy (male and female). In total, including controls, 2,940 mice has been entered into the study. Unfortunately, with the severity of the COVID-19 pandemic in NY we were not able to carry out the Spring 2020 run and as such we were not able to complete the GCR cohorts and could not start the examination of our potential countermeasure. We tried to move the Spring run to the Summer run of 2020 but were not able to schedule this due to the COVID-19 pandemic.

Tissues and serum from 94 animals have been collected for omics analysis as we have passed the 6 and 12 month point for several cohorts. Potential tumor tissue has been isolated and processed from 150 subjects. Suspected tumors are now developing. Furthermore, as a number of animals have become cachexic, currently 28, it is likely that they too have cancers for which total necropsies will be performed to identify tumors not found overtly.

As we are nearing completion of Year 2, some progress is in the numbers of animals irradiated although we are now behind schedule given the impact of COVID-19. Histologic samples and veterinary examination of potential tumors is ongoing. Omics data will not be processed until late Year 3/Year 4 as many of these endpoints require collection only and are processed at a later time to avoid “batch effects” associated with sample processing. As it stands we are about 65% of the way through the animal cohorts.

Bibliography: Description: (Last Updated: 12/14/2023) 

Show Cumulative Bibliography
 
 None in FY 2020
Project Title:  Determining Gender Differences in the Incidence of Lung Adenocarcinoma After Space Radiation Exposure Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 09/01/2018  
End Date: 08/31/2022  
Task Last Updated: 07/22/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Story, Michael D Ph.D. / University of Texas, Southwestern Medical Center 
Address:  Division of Molecular Radiation Biology 
2201 Inwood Rd., Room NC7.206 
Dallas , TX 75235-7320 
Email: michael.story@utsouthwestern.edu 
Phone: 214 648 5557  
Congressional District: 30 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Texas, Southwestern Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lianghao, Ding  Ph.D. University of Texas Southwestern Medical Center, Dallas 
Project Information: Grant/Contract No. 80NSSC18K1676 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Unique ID: 12048 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC18K1676 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
Human Research Program Gaps: (1) Cancer-103:Determine the effects of radiation quality on cancer initiation, promotion, and progression.
(2) Cancer-203:Evaluate the tissue-specific risks of space radiation exposure on cancer outcomes.
(3) Cancer-204:Evaluate the sex-specific risks of space radiation exposure on cancer outcomes.
(4) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
Task Description: Uncertainties in radiation induced lung cancer risk estimation and its associated mortality rates are among the primary factors limiting the number of safe days an astronaut can spend in space. Initial lung cancer risks are based off epidemiological-based modeling and include cohorts such as the atomic bomb survivor life span study (LSS) whose estimates contain large confidence intervals and whose populations may not reflect astronauts on deep space missions. In order to calculate the permissible exposure limit (PEL) for astronauts it is necessary to collect further information on the risk of lung carcinogenesis due to radiation quality differences (relative biological effectiveness--RBE), sex disparities, and how effective biological countermeasures may reduce or mitigate these risks.

The goal of this project is to provide sufficient data to bolster risk estimates and RBE values for lung carcinogenesis from the individual small, intermediate, and heavy charged particles that comprise galactic cosmic rays (GCRs) with doses comparable to what an astronaut may receive on a Mars mission. Additionally we will delineate any sex differences in radiogenic lung cancer risk resulting from space radiation exposure, provide sufficient evidence to validate GC4419, a FDA investigational new drug (IND), as an effective pharmaceutical countermeasure, and mechanistically define the biological processes associated with space radiation induced lung carcinogenesis.

Research Impact/Earth Benefits: There are two areas where this research may benefit life on Earth.

1) Differences in both the incidence of and mortality arising from lung cancer between men and women have long been appreciated, with women generally having higher incidences and mortality rates than men. Epidemiological studies comparing pre- and post-menopausal women treated with hormone replacement therapy (HRT) have demonstrated that female sex hormones both elevated the incidence and aggressiveness at the time of presentation. These effects likely enhance the efficacy of other carcinogens such as radiation or tobacco smoke. We are following the production of estrogen for 8 weeks post-IR (irradiation) to determine whether space radiation is more effective at reducing estrogen via the radioresponse of the mouse ovary. We will follow lung cancer in mice with lower estrogen to determine the impact on ovarian function and risk for radiation-induced lung cancer. We may also consider estrogen replacement to determine how "hormone replacement" alters lung cancer risk from radiation exposure.

2) GC4419 is a radioprotector for radiation-induced mucositis and lung fibrosis from radiation exposure. What is not known, although the preliminary evidence suggests it could, is whether GC4419 has anti-carcinogenic effects. If it does, the potential to reduce the risk for cancer in humans after environmental or diagnostic radiation exposures is compelling.

Task Progress & Bibliography Information FY2019 
Task Progress: As we are nearing completion of Year 1, the only really significant progress is in the numbers of animals irradiated. At the point there has not been an opportunity to collect histologic, enzymatic, or omics data. Indeed, the significance of the representative estrous cycling measurements is not yet clear. Furthermore, many of these endpoints require collection only and are processed at a later time to avoid “batch effects” associated with sample processing.

To date we have irradiated 10 of 19 cohorts of animals based upon radiation type, dose, and sex. Ovaries have been harvested for nearly all cohorts and have been sent to the pathology core for processing and tissue mounting. Estrous cycles have been examined in nearly all groups as well.

Tissues and serum for omics analysis has not yet been collected as we are not at the first 6 month post-irradiation time point.

Bibliography: Description: (Last Updated: 12/14/2023) 

Show Cumulative Bibliography
 
 None in FY 2019
Project Title:  Determining Gender Differences in the Incidence of Lung Adenocarcinoma After Space Radiation Exposure Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 09/01/2018  
End Date: 08/31/2022  
Task Last Updated: 10/30/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Story, Michael D Ph.D. / University of Texas, Southwestern Medical Center 
Address:  Division of Molecular Radiation Biology 
2201 Inwood Rd., Room NC7.206 
Dallas , TX 75235-7320 
Email: michael.story@utsouthwestern.edu 
Phone: 214 648 5557  
Congressional District: 30 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Texas, Southwestern Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lianghao, Ding  Ph.D. University of Texas Southwestern Medical Center, Dallas 
Project Information: Grant/Contract No. 80NSSC18K1676 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Unique ID: 12048 
Solicitation / Funding Source: 2016-2017 HERO NNJ16ZSA001N-SRHHC. Appendix E: Space Radiobiology and Human Health Countermeasures Topics 
Grant/Contract No.: 80NSSC18K1676 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
Human Research Program Gaps: (1) Cancer-103:Determine the effects of radiation quality on cancer initiation, promotion, and progression.
(2) Cancer-203:Evaluate the tissue-specific risks of space radiation exposure on cancer outcomes.
(3) Cancer-204:Evaluate the sex-specific risks of space radiation exposure on cancer outcomes.
(4) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
Task Description: The primary risk factor limiting the amount of time an astronaut can spend in flight is the risk of cancer induction resulting from the unique radiations inherent to the deep space environment. One strategy for mitigating radiation induced carcinogenesis is to provide biological countermeasures that mitigate radiation injury and cancer induction. To date the only Food and Drug Administration (FDA) approved radioprotector is the free radical scavenger, Amifostine; however, concerns about toxicity and reports of severe anaphylactic reactions to this drug prevent its use in spaceflight. Therefore, there is a need to determine and validate appropriate biological countermeasures to mitigate space radiation carcinogenesis, thereby increasing the amount of time astronauts can safely spend in space. In the proposed studies we will evaluate the radio protective potential of GC4419, a novel superoxide dismutase mimetic developed by Galera Therapeutics (St. Louis, MO), in mitigating space radiation carcinogenesis. Due to its efficacy in Phase 1 clinical trials and pre-clinical data generated by our group, GC4419 is currently being fast tracked into FDA Phase II, human clinical trials as a radioprotector for patients undergoing chemoradiation therapy for the treatment of head and neck cancer. Not only does GC4419 reduce the frequency of radiation induced adverse effects, pre-clinical data suggest it has potent anti-carcinogenic and anti-tumor effects as well. Therefore, GC4419 represents a safe, clinically tested countermeasure to reduce radiation injury. In the proposed studies, we will evaluate the efficacy of GC4419 in preventing space radiation induced carcinogenesis focusing specifically on the lung as a primary tumor site.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2018 
Task Progress: New project for FY2018.

Bibliography: Description: (Last Updated: 12/14/2023) 

Show Cumulative Bibliography
 
 None in FY 2018