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PubMedDate not supplied

Changed adhesion molecule profile of Ewing tumor cell lines and xenografts under the influence of ionizing radiation.

BACKGROUND: Adhesion molecules are involved in cell-cell and cell-matrix interactions and may be informative to characterize intercellular mechanisms of invasion and metastasis. This study was performed to characterize radiation-induced changes in the adhesion molecule profile of Ewing tumor subpopulations on a single cell level. MATERIALS AND METHODS: In the present study, two Ewing tumors were characterized in vitro 4, 24 and 72 hours after radiation with 5 Gy and in vivo in a xenograft model 4, 6 and 15 days after radiation with 30 Gy, together with non-irradiated controls, by five parameter flow cytometry. Directly fluorescence-conjugated antibodies that were directed against adhesion molecules (LFA-1 (CD11a), HCAM (CD44), VLA-2 (CD49b), ICAM-1 (CD54), NCAM (CD56), LECAM-1 (CD62L) and CD86) were used. Annexin V and 7-AAD were used to characterize radiation-induced apoptosis. RESULTS: Tumor cell subpopulations were identified by the expression of adhesion molecules, apoptotic markers and DNA content. Heterogeneous changes of the adhesion molecule profile were identified on tumor cell subpopulations after radiation. The expression of CD11a and CD62L correlated with the expression of apoptosis-associated markers. CONCLUSION: The changes of flow cytometric profile under radiation may potentially correlate with a changed metastatic potential of tumor cell subpopulations.

Animals↗
PubMedDate not supplied

Diminished cellular and humoral immunity in workers occupationally exposed to low levels of ionizing radiation.

BACKGROUND: It has been reported that subgroups of T-lymphocytes are affected at different levels and different cell groups of immune system give different responses in individuals exposed to long-term ionizing radiation. The aim of this study was to investigate the effect of occupational exposure to low levels of ionizing radiation in selected indices of cellular and humoral immunity in radiology workers. METHODS: Level of subgroups of peripheral blood lymphocytes, complements (C(3), C(4)), and total immunoglobulins (IgG, IgA, IgM) were analyzed in 50 radiology workers occupationally exposed to low levels of ionizing radiation and 35 age-matched healthy controls. RESULTS: CD4(+) T lymphocyte (T-helper) levels were determined as significantly low in radiology workers exposed to ionizing radiation compared with controls (p <0.05). There were no statistically significant differences in groups in terms of other subgroups of lymphocytes (p >0.05). In addition, levels of serum total IgG, IgA, IgM, C(3,) and C(4) were determined as significantly lower in workers exposed to ionizing radiation compared with controls (p <0.001). Total IgA and IgM levels in radiology workers who were smokers were determined as significantly lower compared with non-smoking radiology workers (p >0.05). CONCLUSIONS: Levels of CD4(+) T lymphocytes and humoral immune response (total immunoglobulins and complements) were determined as weaker in workers exposed to low levels of ionizing radiation compared with controls, indicating the importance of taking appropriate measures to protect radiology workers from exposure to ionizing radiation and for these workers to avoid smoking. Further studies are needed for determining the appropriateness of periodic check-ups of immune functions and the most efficient and cost-effective ways of monitoring immune functions in radiology workers for detecting early changes in the immune system.

Adult↗
PubMed1997

[Evaluation of technogenic radiation exposures from ecological and physiological points of view].

Many years' experience with complex supervision of the environmental radiation situation, the specific features of the population's physiological and health status after radiation accidents (the Chernobyl, Kyshtym and other accidents). The paper emphasized the necessity of having a knowledge of the specific features of the influence of a radiation factor (and its components) on establishing the radiation dose for the population due to the environmental peculiarities of the radiation background in different regions and abnormal zones of the Earth. The paper provides evidence for the need to apply an environmental and physiological approach to working out the standards of radiation doses for the inhabitants of post-accident polluted areas. To this end, a concept of the regional standard of exposure is proposed for different regions of the Earth with regard to the specific natural radiation background, technogenic and medical "additives" on making diagnostic and therapeutical efforts by using X-rays and radiation therapy. A new concept is offered to develop the life-support systems in the areas exposed to radiation contamination, whose main goal is to minimize radiation exposures with regard of data on each area-specific data on the regional standard of the pre-accident radiation background, technogenic background, medical additives and prediction of future radiation doses. Exposure of the population to radiation is minimized by reasonably operating its components and making special life regimens in the contaminated areas.

Background Radiation↗
PubMed2006

Comparison of germanium oxide fibers with silica and sapphire fiber tips for transmission of erbium: YAG laser radiation.

BACKGROUND AND OBJECTIVES: Endoscopic applications of the Erbium:YAG laser have been limited due to the lack of a suitable optical fiber delivery system. The purpose of this study was to compare the transmission of Er:YAG laser radiation through germanium oxide trunk fibers with silica and sapphire fiber tips for potential use in contact tissue ablation during endoscopy. STUDY DESIGN/MATERIALS AND METHODS: Er:YAG laser radiation with a wavelength of 2.94 microm, pulse length of 300 microseconds, pulse energies from 5 to 1,360 mJ, coupled into pulse repetition rates of 3-10 Hz, was through 1-m-long germanium oxide fibers with either 1-cm-long, 550-microm-diameter silica or sapphire tips. RESULTS: Transmission through the germanium oxide/sapphire fibers measured 65+/-5% compared with 55+/-4% for the germanium oxide/silica fibers (P<0.05). The damage threshold for the hybrid fibers averaged 309+/- 44 mJ and 126+/-43 mJ, respectively (n = 7 fibers each) (P<0.05). The highest pulse energies transmitted through the fibers were 700 mJ and 220 mJ, respectively. CONCLUSIONS: Improved index-matching of the trunk fiber and fiber tip at 2.94 microm resulted in higher transmission and damage thresholds for the germanium oxide/sapphire fibers. The germanium oxide/sapphire fiber may represent a promising mid-infrared optical fiber delivery system for use in endoscopic applications of the Er:YAG laser requiring a flexible, biocompatible, and robust fiber delivery system for contact tissue ablation.

Aluminum Oxide↗
PubMed2004

Hybrid germanium/silica optical fibers for endoscopic delivery of erbium:YAG laser radiation.

BACKGROUND AND OBJECTIVES: Endoscopic applications of the erbium (Er):YAG laser have been limited due to the lack of an optical fiber delivery system that is robust, flexible, and biocompatible. This study reports the testing of a hybrid germanium/silica fiber capable of delivering Er:YAG laser radiation through a flexible endoscope. STUDY DESIGN/MATERIALS AND METHODS: Hybrid optical fibers were assembled from 1-cm length, 550-microm core, silica fiber tips attached to either 350- or 425-microm germanium oxide "trunk" fibers. Er:YAG laser radiation (lambda = 2.94 microm) with laser pulse lengths of 70 and 220 microseconds, pulse repetition rates of 3-10 Hz, and laser output energies of up to 300 mJ was delivered through the fibers for testing. RESULTS: Maximum fiber output energies measured 180+/-30 and 82+/-20 mJ (n = 10) under straight and tight bending configurations, respectively, before fiber interface damage occurred. By comparison, the damage threshold for the germanium fibers without silica tips during contact soft tissue ablation was only 9 mJ (n = 3). Studies using the hybrid fibers for lithotripsy also resulted in fiber damage thresholds (55-114 mJ) above the stone ablation threshold (15-23 mJ). CONCLUSIONS: Hybrid germanium/silica fibers represent a robust, flexible, and biocompatible method of delivering Er:YAG laser radiation during contact soft tissue ablation. However, significant improvement in the hybrid fibers will be necessary before they can be used for efficient Er:YAG laser lithotripsy.

Endoscopes↗
PubMed2000

Prevention of local recurrence after surgical debulking of nodal and subcutaneous melanoma deposits by hypofractionated radiation.

BACKGROUND: Local recurrence (LR) after surgical debulking of nodal or subcutaneous melanoma deposits defeats the purpose of operation and may worsen prognosis if the procedure was performed for stage III disease. To decrease LR rates in this setting, we extended the previously described role of hypofractionated radiation for melanoma deposits of the neck to all situations where the patient was felt to be at high risk for postoperative relapse after resection of bulky disease. METHODS: Hypofractionated external beam radiation was administered in 6-Gy doses for 5 fractions (total dose 30 Gy, given over a median of 15 elapsed days) to 42 resected melanoma deposit sites in 41 patients. RESULTS: Stages of the 41 patients at the time of treatment were: 22 stage III and 19 stage IV. All patients had complete gross resection of disease at the radiation site before radiation. Mean time between operation and initiation of radiation was 4 weeks. The 42 sites of treatment included 27 neck, 9 axilla, 3 groin, and 3 subcutaneous deposits. There were no treatment-related deaths; side effects were minimal and self-limited. Transient erythema, desquamation, fibrosis, telangiectasias, and mucositis, parotiditis, and xerostomia (for head and neck radiation) were reported, but no patient required interruption of therapy for these events. Of the 42 treated sites, only 2 recurred in the treatment field (one neck, one axilla) during the mean follow-up time of 22.4 months, for a treatment failure rate of 4.8%. This represents improved local control compared with patients treated with surgery alone at our institution and with published recurrence rates. CONCLUSIONS: The addition of hypofractionated radiation therapy after resection of nodal and subcutaneous melanoma deposits at a variety of sites is a rapid and well-tolerated method of providing excellent local control.

Adult↗
PubMed1999

Safe pulmonary resection after chemotherapy and high-dose thoracic radiation.

BACKGROUND: Pulmonary resection after high-dose thoracic irradiation is reported to be associated with a high morbidity and mortality, and has been considered to be prohibitive. METHODS: We report safe pulmonary resection in 19 consecutive patients receiving neoadjuvant therapy that included greater than 59 Gy thoracic radiation. The mean thoracic radiation dose was 61.8 Gy (range 59.5-66.5) and mean age was 52 years (range 36-72 years). Cell type was adenocarcinoma (6), squamous (7), and other non-small cell lung cancer (NSCLC) (6). Sixteen of 19 patients received concurrent chemotherapy. Median time from end of treatment to surgical resection was 89 days (range 22-258 days). Surgical resection included 13 lobectomies and six pneumonectomies (four right, two left). RESULTS: A complete pathologic response was seen in 8 of 19 (42%) patients. Three patients required intraoperative transfusion of blood. Mean intensive care unit stay was 2.0 days (range 1-8 days), and mean length of stay (LOS) was 8.0 days (range 3-18 days). There were four postoperative complications; one bronchopulmonary fistula, one subarachnoid-pleural fistula, and 2 patients with prolonged atelectasis. There was no incidence of acute respiratory distress syndrome (ARDS) or operative mortality. CONCLUSIONS: Pulmonary resection, including pneumonectomy, after chemotherapy and high-dose thoracic radiation may be performed safely with a low rate of intraoperative and postoperative complications.

Adenocarcinoma↗
PubMed2003

Scleredema adultorum of Buschke treated with radiation.

BACKGROUND: Scleredema adultorum of Buschke is an uncommon skin condition that may accompany diabetes mellitus. Current therapeutic options are poor, with only case reports and small series supporting their use. OBSERVATION: We describe 3 patients with severe restrictive scleredema associated with type 2 diabetes mellitus who responded to radiation therapy after other treatments had failed. Angle of shoulder abduction was used as an objective measurement of improvement, while the patients rated several subjective areas, including arm range of motion, ease of performing daily tasks, ease of breathing, and neck thickening. Objective improvement tended to plateau over time but remained well above baseline. The duration of subjective improvement was variable, lasting from a few months to the end of the observation time of 2 1/2 years. CONCLUSION: Though not consistently durable in its effect, radiation therapy appears to be a viable therapeutic option in extreme cases of this difficult-to-treat disease.

Follow-Up Studies↗
PubMed1999

5-HT3 receptor antagonists ameliorate emesis in the ferret evoked by neutron or proton radiation.

BACKGROUND: Nausea and vomiting produced by sub-lethal doses of X- or gamma-rays can be ameliorated by serotonin subtype-three (5-hydroxytryptamine; 5-HT3) receptor antagonists. The effectiveness of these anti-emetics on blocking the emetic responses induced by fission neutron or proton radiation exposure was evaluated in the ferret animal model. HYPOTHESIS: 5-HT3 receptor antagonists or bilateral vagotomy will ameliorate that emesis evoked by fission neutrons or protons. METHODS: Groups of ferrets were exposed to whole-body or head-shielded radiations of varying qualities: fission spectrum neutons, high-energy protons, or gamma-rays. Prior to that exposure, some groups were either vagotomized or received subcutaneous (s.c.) or oral (p.o.) treatment with various doses of the 5-HT3 receptor antagonist antiemetics eusatron and ondansetron. RESULTS: We demonstrated that both eusatron and ondansetron effectively abolished the emesis normally induced by 2-Gy doses of either 60Co gamma or neutron:gamma, mixed-field irradiation, the latter with a neutron-to-total dose ratio (Dn/Dt) of 0.9+/-2% (%SD). Different routes of delivery of the anti-emetics yielded different degrees of inhibition of the emetic responses; p.o. treatment was less efficacious than s.c. treatment for the emesis to fission neutrons. Eusatron was significantly more effective than ondansetron on a mg x kg(-1) basis. Bilateral vagotomy also attenuated or abolished the emetic responses to the mixed-field neutron exposures. Furthermore, emesis induced by exposure to 2.5 Gy of 200-MeV protons was effectively abolished by ondansetron. CONCLUSION: These results are consistent with the concept that similar physiological and pharmacological mechanisms underlie the emetic responses to different qualities of radiation.

Administration, Oral↗
PubMed2002

Increased expression of Fas on human epidermal cells after in vivo exposure to single-dose ultraviolet (UV) B or long-wave UVA radiation.

BACKGROUND: Apoptosis has been proposed to act as an important mechanism for eliminating keratinocytes that have been irreversibly damaged by ultraviolet (UV) irradiation. One way to induce apoptosis in keratinocytes is through activation of the cell surface receptor Fas (CD95), either with the ligand (FasL) or directly with UV radiation. OBJECTIVES: To investigate the regulation of Fas and FasL expression in human skin and the formation of apoptotic cells after in vivo exposure to UVB or long-wave UVA radiation. METHODS: Volunteers were irradiated with either 3 minimal erythema doses (MED) of UVB (n = 6) or 3 MED of long-wave UVA (n = 6) on buttock skin 12, 24 and 72 h before skin punch biopsies were taken. Expression of Fas and FasL was demonstrated by immunohistochemistry on cryostat sections. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine triphosphate nick-end labelling reaction. RESULTS: In five of six subjects, exposure to UVB radiation resulted in increased homogeneous expression of Fas on epidermal cells, with greatest expression at 24 and 72 h after irradiation. In all subjects, exposure to long-wave UVA resulted in increased homogeneous expression of Fas on epidermal cells, with greatest expression at 12 h after irradiation. In five of six subjects, exposure to UVB radiation resulted in temporarily decreased expression of FasL, but after 72 h the expression of FasL had returned to the preirradiation level. The expression of FasL on epidermal cells after exposure to long-wave UVA showed considerable variation. UVB irradiation was a stronger inducer of epidermal apoptosis than was UVA irradiation. The number of apoptotic epidermal cells did not correlate with expression of Fas or FasL. CONCLUSIONS: In human skin the expression of Fas on epidermal cells increases after in vivo exposure to UVB or long-wave UVA. Exposure to UVB causes a temporary decrease in the expression of FasL on epidermal cells.

Adult↗
PubMed2005

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation.

BACKGROUND: During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication- and transcription-blocking lesions. RESULTS: Cultures enriched for neonatal rat cardiac myocytes (CM) or fibroblasts were subjected to any one of the three stressors. Affymetrix microarrays, analysed with Linear Modelling on Probe Level, were used to determine gene expression patterns at 24 hours after (the start of) treatment. The numbers of differentially expressed genes after UV were considerably higher than after IR or MS. Remarkably, after all three stressors the predominant gene expression response in CM-enriched fractions was up-regulation, while in fibroblasts genes were more frequently down-regulated. To investigate the activation or repression of specific cellular pathways, genes present on the array were assigned to 25 groups, based on their biological function. As an example, in the group of cholesterol biosynthesis a significant proportion of genes was up-regulated in CM-enriched fractions after MS, but down-regulated after IR or UV. CONCLUSION: Gene expression responses after the types of cellular stress investigated (MS, IR or UV) have a high stressor and cell type specificity.

Animals↗
PubMed2004

Anti-tumor effect of combination therapy with intratumoral controlled-release paclitaxel (PACLIMER microspheres) and radiation.

BACKGROUND: Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism. METHODS: Orthotopic LNCaP tumors were injected with 40% PACLIMER Microspheres (40% loading; w:w) when tumors were 100-200 mm(3). Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm(3). Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time. RESULTS: Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P < 0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres. CONCLUSIONS: A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers.

Animals↗
PubMed2001

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.

Adult↗
PubMed1995

Malignant melanoma and other second cutaneous malignancies in cutaneous T-cell lymphoma. The influence of additional therapy after total skin electron beam radiation.

BACKGROUND: Previous large studies have shown that patients with cutaneous T-cell lymphoma are at increased risk for basal cell carcinoma and squamous cell carcinoma, and anecdotal case reports have suggested an association with malignant melanoma. It has been postulated that the exposure of cutaneous structures to potentially carcinogenic therapies, such as ionizing radiation or alkylating agents, might be causally associated with the development of these second cutaneous malignancies, but, to date, no study has directly addressed this issue. The purpose of this study was to evaluate the occurrence of second cutaneous malignancies in a group of patients with cutaneous T-cell lymphoma treated with total skin electron beam therapy and to examine the additional effects of oral psoralen with UV-A phototherapy, topical mechlorethamine hydrochloride therapy, and further radiation therapy. One hundred sixty-four patients with cutaneous T-cell lymphoma who had received total skin electron beam therapy between 1974 and 1990 were identified, and information was abstracted from their records. RESULTS: Six patients developed malignant melanoma 12 to 95 months after total skin electron beam therapy. Of the six patients, three had received oral psoralen with UV-A as additional therapy and two had received topical mechlorethamine. None had received additional radiation therapy. Twenty-four patients developed more than 37 basal cell carcinomas and 34 squamous cell carcinomas from 11 months to more than 10 years after total skin electron beam therapy. Of the 24 patients, 15 had received oral psoralen with UV-A and 12 had received mechlorethamine as additional therapy. Additional radiation therapy had been administered to nine patients. During a median follow-up of 6 years, no patients died of any second cutaneous malignancy. CONCLUSION: We found a high rate of both melanoma and nonmelanoma skin cancer. The additional use of mechlorethamine or oral psoralen plus UV-A, but not radiation, was significantly associated with the development of basal cell carcinoma and squamous cell carcinoma, but not malignant melanoma.

Adult↗
PubMed1999

Photoablation of bone by excimer laser radiation.

BACKGROUND AND OBJECTIVES: The aim of the present study was to compare the usefulness of mechanical osteotomy tools and common laser systems with the ultraviolet (UV) laser in the field of the central nervous system and its bony capsule. STUDY DESIGN/MATERIALS AND METHODS: The cranial bones of 42 living rats were treated with UV laser radiation with wavelengths of 193 nm and 248 nm. The morphology and physical effects were evaluated by means of optical and scanning electron microscopy. RESULTS: This study shows the special characteristics of excimer versus infrared lasers or mechanical tools, such as high precision, no thermic damage, little depth effect, and no delay of healing processes. CONCLUSION: The excimer laser is an interesting instrument for microsurgery of bones in orthopaedics, neurosurgery, and otolaryngology.

Animals↗
PubMed1995

Plastic hollow waveguides: properties and possibilities as a flexible radiation delivery system for CO2-laser radiation.

BACKGROUND AND OBJECTIVES: One significant inconvenience of the CO2 laser is the lack of flexible fibers essential for endoscopic applications. The goal of this study is to test the feasibility of hollow waveguides in view of a practical use in medicine. STUDY DESIGN/MATERIALS AND METHODS: Various types of plastic hollow waveguides for flexible delivery of CO2 laser radiation were examined. The transmission losses, divergence angle, damage threshold, and input and output beam profiles were determined. The interaction process between radiation transmitted through these guides with soft as well as hard tissues was studied. RESULTS: Plastic hollow waveguides can transmit high power (up to 50 W) with low losses (straight guide 1 dB/m) even through bendings. The divergence angle is < 13 degrees. Cutting quality and extent of thermal damage are comparable to incisions performed with a free laser beam. CONCLUSION: The results of this study show good cutting quality and durability of these flexible plastic hollow waveguides, which render possible to deliver CO2 radiation in the power range needed for most surgical applications with affordable transmission losses. Plastic hollow waveguides are, therefore, a real alternative to replace the mirror arms.

Animals↗
PubMed2003

The CUSP DeltaNp63alpha isoform of human p63 is downregulated by solar-simulated ultraviolet radiation.

BACKGROUND: In normal human keratinocytes, a p53-like protein, DeltaNp63alpha, also known as CUSP, is constitutively and abundantly expressed. The significant constitutive expression of DeltaNp63alpha in stratified epithelium has been proposed to maintain the proliferative capacity of basal cells, blocking the consequences of inappropriate p53 activation. OBJECTIVE: To determine the response of keratinocyte DeltaNp63alpha to ultraviolet radiation (UVR), a stimulus for p53 activation. METHODS: Cultured normal human keratinocytes were exposed to graded doses of solar-simulated UVR. The expression of DeltaNp63alpha protein and mRNA were measured with Western and Northern blotting. Normal mouse skin was exposed to UVR, and DeltaNp63alpha expression assessed with immunohistochemistry. RESULTS: Increasing doses of UVR virtually shut off DeltaNp63alpha protein and mRNA expression in cultured normal human keratinocytes and in normal mouse skin in vivo. CONCLUSION: This study supports the hypothesis that in situations where p53 activation is desirable, as with DNA-damaging UVR, DeltaNp63alpha downregulation occurs and may possibly allow for better target gene transcription by p53.

Animals↗
PubMed2002

An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation.

BACKGROUND: There are large geographic gradients in mortality rates for a number of cancers in the U.S. (e.g., rates are approximately twice as high in the northeast compared with the southwest). Risk factors such as diet fail to explain this variation. Previous studies have demonstrated that the geographic distributions for five types of cancer are related inversely to solar radiation. The purpose of the current study was to determine how many types of cancer are affected by solar radiation and how many premature deaths from cancer occur due to insufficient ultraviolet (UV)-B radiation. METHODS: UV-B data for July 1992 and cancer mortality rates in the U.S. for between 1970-1994 were analyzed in an ecologic study. RESULTS: The findings of the current study confirm previous results that solar UV-B radiation is associated with reduced risk of cancer of the breast, colon, ovary, and prostate as well as non-Hodgkin lymphoma. Eight additional malignancies were found to exhibit an inverse correlation between mortality rates and UV-B radiation: bladder, esophageal, kidney, lung, pancreatic, rectal, stomach, and corpus uteri. The annual number of premature deaths from cancer due to lower UV-B exposures was 21,700 (95% confidence interval [95% CI], 20,400-23,400) for white Americans, 1400 (95% CI, 1100-1600) for black Americans, and 500 (95% CI, 400-600) for Asian Americans and other minorities. CONCLUSIONS: The results of the current study demonstrate that much of the geographic variation in cancer mortality rates in the U.S. can be attributed to variations in solar UV-B radiation exposure. Thus, many lives could be extended through increased careful exposure to solar UV-B radiation and more safely, vitamin D3 supplementation, especially in nonsummer months.

Adult↗