Search NASA⌕ Search

SEARCH · Search NASA

Results for “MELANOMAS”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

7 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

NASA Discipline Radiation Health↗
NASA NTRS2002

Shedding light on proteins, nucleic acids, cells, humans and fish

I was trained as a physicist in graduate school. Hence, when I decided to go into the field of biophysics, it was natural that I concentrated on the effects of light on relatively simple biological systems, such as proteins. The wavelengths absorbed by the amino acid subunits of proteins are in the ultraviolet (UV). The wavelengths that affect the biological activities, the action spectra, also are in the UV, but are not necessarily parallel to the absorption spectra. Understanding these differences led me to investigate the action spectra for affecting nucleic acids, and the effects of UV on viruses and cells. The latter studies led me to the discovery of the important molecular nature of the damages affecting DNA (cyclobutane pyrimidine dimers) and to the discovery of nucleotide excision repair. Individuals with the genetic disease xeroderma pigmentosum (XP) are extraordinarily sensitive to sunlight-induced skin cancer. The finding, by James Cleaver, that their skin cells were defective in DNA repair strongly suggested that DNA damage was a key step in carcinogenesis. Such information was important for estimating the wavelengths in sunlight responsible for human skin cancer and for predicting the effects of ozone depletion on the incidence of non-melanoma skin cancer. It took experiments with backcross hybrid fish to call attention to the probable role of the longer UV wavelengths not absorbed by DNA in the induction of melanoma. These reflections trace the biophysicist's path from molecules to melanoma.

NASA Discipline Radiation Health↗
NASA NTRS1993

Measuring the metastatic potential of cancer cells

Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

Morrison, Dennis R.↗
NASA NTRS2000

Particle irradiation induces FGF2 expression in normal human lens cells

Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

NASA Discipline Radiation Health↗
NASA NTRSDate not supplied

Assessing Long-Term Health (LTH) Outcomes in Astronauts

NASA has linked potential Long-Term Health (LTH) risks of astronauts to their spaceflight experience, including the effects of space radiation, microgravity, and stressors such as isolation, sleep deprivation, and stress. Therefore, assessing the LTH outcomes for astronauts exposed to these hazards becomes a critical investigation in ensuring any deleterious effects are minimal. Prior research conducted into LTH outcomes of astronauts has not revealed increases in non-accidental mortality rates when compared to the U.S. general population, analog healthy cohorts, and professional athletes. One study did report an increased incidence of non-fatal cardiovascular disease events (Hazard Ratio=2.41, 95% Confidence Interval 1.26 to 4.63). Additional evidence indicates that astronauts may have increases in incidences of melanoma, prostate, and hematologic cancers, though the former is consistent with rates observed among aircraft pilots and the latter two are likely caused by detection bias due to increased screening on former astronauts.

long term health↗
NASA NTRSDate not supplied

Long-Term Health Risk Quantification

Astronauts face hazards during spaceflight, including space radiation exposure, isolation and confinement, traveling far distances from Earth, reduced gravity levels, and closed and hostile environments. These hazards drive the definition of human health and performance risks associated with spaceflight. NASA’s Human System Risk Board maintains the human spaceflight risk posture for in-mission risks, as well as post-flight, Long-Term Health (LTH)risks potentially occurring later in the astronaut’s life. LTH risk encompasses the timeframe from immediately post-flight, through the rest of an astronaut’s career, through retirement, and until death. Possible LTH risk outcomes include the time and interventions needed for the astronaut to return to preflight physiological states after experiencing spaceflight hazards and recovery from any in-mission medical events that persist into the post-flight timeframe. It includes chronic complications that may arise due to experiencing in-flight medical conditions or injuries and medical conditions that occur later in life with a higher probability of occurrence or with more severity because of their spaceflight exposure. Finally, LTH risk outcomes can also include a reduction in life expectancy due to spaceflight exposures. There have been 144 medical conditions identified by NASA’s Lifetime Surveillance of Astronaut Health team to be associated with LTH risk. Epidemiological studies have been performed for some of these conditions to determine if astronauts suffer from an increased prevalence or severity of the condition due to their spaceflight experience compared to a comparable cohort .Differences in astronaut mortality or morbidity due to spaceflight experience were not detected in several of these studies. There were two cases where a modest increase in the incidence rate of astronaut LTH outcomes was detected. The first suggested an increase in the incidence of melanoma cases in astronauts, where the number of cases in astronauts were similar to the elevated number of cases observed in airplane pilots. The second provided some evidence of elevated numbers of cardiovascular disease events in astronauts compared to an appropriate healthy comparator cohort, which may warrant additional investigation. The lack of detection of LTH risk outcomes should not ease concerns about astronaut LTH. The studies highlighted here constitute only a small portion of the potential LTH conditions that could occur. Once epidemiological studies are performed on all conditions, significant findings may be detected. The analysis of astronaut LTH also suffers from limited numbers of data points because of the limited numbers of astronauts overall and the even fewer who have reached an age where LTH outcomes may begin to manifest. As shuttle and ISS astronauts begin to age and increase the feasibility of analysis, LTH outcomes may be detected. An application of risk quantification is the use of risk metrics within trade studies for resource prioritization and decision making. Trade studies regarding countermeasures to LTH risk outcomes would benefit from a quantification of LTH risk. NASA has ground-based processes in place such as astronaut screening and access to continuous medical monitoring and care during and after their astronaut career which are the main methods for mitigating LTH risk. In-mission countermeasures, such as acceptable levels of medical care and available countermeasures to counter spaceflight related physiological decrements, can mitigate a poor health and performance status immediately post-flight. Identifying appropriate risk metrics, obtaining valid quantities for them, and tying them to LTH countermeasures are necessary steps for realizing their use in trade studies. This presentation will highlight the challenges associated with the identification, quantification, and utilization of LTH risk metrics

Beth Lewandowski↗
NASA NTRS2002

Tensile stress stimulates microtubule outgrowth in living cells

Cell motility is driven by the sum of asymmetric traction forces exerted on the substrate through adhesion foci that interface with the actin cytoskeleton. Establishment of this asymmetry involves microtubules, which exert a destabilising effect on adhesion foci via targeting events. Here, we demonstrate the existence of a mechano-sensing mechanism that signals microtubule polymerisation and guidance of the microtubules towards adhesion sites under increased stress. Stress was applied either by manipulating the body of cells moving on glass with a microneedle or by stretching a flexible substrate that cells were migrating on. We propose a model for this mechano-sensing phenomenon whereby microtubule polymerisation is stimulated and guided through the interaction of a microtubule tip complex with actin filaments under tension.

NASA Discipline Cell Biology↗