PURPOSE: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. RESULTS: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. CONCLUSIONS: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

• MeSH
• cisplatina terapeutické užití   MeSH
• kostní dřeň účinky záření   MeSH
• lidé MeSH
• nádory děložního čípku * diagnostické zobrazování   farmakoterapie   patologie   radioterapie   MeSH
• pozitronová emisní tomografie MeSH
• radioterapie řízená obrazem MeSH
• radioterapie s modulovanou intenzitou * škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cisplatina MeSH

Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.

• MeSH
• dávka záření MeSH
• dospělí MeSH
• ionizující záření * MeSH
• kostní dřeň patologie   účinky záření   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• lymfom diagnóza   etiologie   MeSH
• odds ratio MeSH
• radiační expozice škodlivé účinky   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The increasing risk of acute large-scale exposure of ionising irradiation on the population underlines the necessity of developing effective radioprotective and mitigating agents. The aim of this work was to investigate the effect of sodium orthovanadate pre-treatment on mice exposed to high doses of gamma rays (from 5 to 13 Gy). The determination of median lethal dose within 30 days confirmed that orthovanadate applied to total-body-irradiated mice intra-peritoneally has a radioprotective but not a mitigating effect. With orthovanadate pre-treatment, the composition of cellularity in the bone marrow improved substantially and the main lymphocyte populations restored during the first month after irradiation. These findings contribute to 'gap-filling' in radioprotective effects and demonstrate the importance of haematological parameters in radiation-response prediction.

• MeSH
• B-lymfocyty účinky léků   MeSH
• buňky NK účinky léků   MeSH
• celotělové ozáření * MeSH
• inhibitor p21 cyklin-dependentní kinasy metabolismus   MeSH
• ionizující záření MeSH
• kostní dřeň účinky léků   účinky záření   MeSH
• lymfocyty účinky léků   účinky záření   MeSH
• makrofágy metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• průtoková cytometrie MeSH
• radioprotektivní látky farmakologie   MeSH
• T-lymfocyty účinky léků   MeSH
• vanadáty farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Cdkn1a protein, mouse MeSH Prohlížeč
• inhibitor p21 cyklin-dependentní kinasy MeSH
• nádorový supresorový protein p53 MeSH
• radioprotektivní látky MeSH
• Trp53 protein, mouse MeSH Prohlížeč
• vanadáty MeSH

BACKGROUND: To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity modulated radiation therapy (IMRT) yields similar dosimetric results compared to custom ABM-sparing IMRT for cervical cancer patients. METHODS: We sampled 62 cervical cancer patients with pre-treatment FDG-PET/CT in training (n=32) or test (n=30) sets. ABM was defined as the subvolume of the pelvic bone marrow (PBM) with standardized uptake value (SUV) above the mean on the average FDG-PET image (ABMAtlas) vs. the individual's PET (ABMCustom). Both were deformed to the planning CT. Overlap between the two subvolumes was measured using the Dice coefficient. Three IMRT plans designed to spare PBM, ABMAtlas, or ABMCustom were compared for 30 test patients. Dosimetric parameters were used to evaluate plan quality. RESULTS: ABMAtlas and ABMCustom volumes were not significantly different (p=0.90), with a mean Dice coefficient of 0.75, indicating good agreement. Compared to IMRT plans designed to spare PBM and ABMCustom, ABMAtlas-sparing IMRT plans achieved excellent target coverage and normal tissue sparing, without reducing dose to ABMCustom (mean ABMCustom dose 29.4Gy vs. 27.1Gyvs. 26.9Gy, respectively; p=0.10); however, PTV coverage and bowel sparing were slightly reduced. CONCLUSIONS: Atlas-based ABM sparing IMRT is clinically feasible and may obviate the need for customized ABM-sparing as a strategy to reduce hematologic toxicity.

• Klíčová slova
• (18)F-FDG PET/CT, Active bone marrow, Atlas-based, Radiotherapy planning,
• MeSH
• celková dávka radioterapie MeSH
• dospělí MeSH
• fluorodeoxyglukosa F18 MeSH
• kostní dřeň účinky záření   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory děložního čípku radioterapie   MeSH
• PET/CT MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• radioterapie s modulovanou intenzitou škodlivé účinky   metody   MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorodeoxyglukosa F18 MeSH

We examined the effect of epidermal growth factor (EGF) treatment in mice that received bone marrow transplantation (BMT) after 11 Gy whole-body irradiation. C57Bl/6 mice were divided into three treatment groups: 0 Gy; 11 Gy ((60)Co, single dose, 0.51 Gy/min) with BMT (5 × 10(6) bone marrow cells isolated from green fluorescent protein syngeneic mice, 3-4 h postirradiation); and 11 Gy with BMT and EGF (2 mg/kg applied subcutaneously 1, 3 and 5 days postirradiation). Survival data were collected. Bone marrow, peripheral blood count and cytokines, gastrointestine and liver parameters and migration of green fluorescent protein-positive cells were evaluated at 63 days postirradiation. Epidermal growth factor increased survival of irradiated animals that received BMT from 10.7 to 85.7% at 180 days postirradiation. In the BMT group, we found changes in differential bone marrow and blood count, plasma cytokine levels, gastrointestinal tissues and liver at 63 days postirradiation. These alterations were completely or in some parameters at least partially restored by epidermal growth factor. These findings indicate that epidermal growth factor, administered 1, 3 and 5 days postirradiation in combination with bone marrow transplantation, significantly improves long-term prognosis.

• MeSH
• apoptóza účinky léků   účinky záření   MeSH
• bezpečnost MeSH
• časové faktory MeSH
• celotělové ozáření škodlivé účinky   MeSH
• cytokiny krev   MeSH
• epidermální růstové faktory farmakologie   MeSH
• kostní dřeň účinky léků   imunologie   účinky záření   MeSH
• mitóza účinky léků   účinky záření   MeSH
• myši MeSH
• počet buněk MeSH
• radiační poranění krev   farmakoterapie   patologie   terapie   MeSH
• slezina účinky léků   patologie   účinky záření   MeSH
• střeva účinky léků   patologie   účinky záření   MeSH
• transplantace kostní dřeně * MeSH
• velikost orgánu účinky léků   účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• epidermální růstové faktory MeSH

This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF), in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

• MeSH
• akutní radiační syndrom farmakoterapie   patologie   MeSH
• časové faktory MeSH
• faktor stimulující kolonie granulocytů biosyntéza   terapeutické užití   MeSH
• interleukin-3 terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kostní dřeň patologie   účinky záření   MeSH
• lidé MeSH
• membránové proteiny terapeutické užití   MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• růstový faktor kmenových buněk terapeutické užití   MeSH
• thrombopoetin terapeutické užití   MeSH
• únik radioaktivních látek MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• faktor stimulující kolonie granulocytů MeSH
• flt3 ligand protein MeSH Prohlížeč
• interleukin-3 MeSH
• membránové proteiny MeSH
• rekombinantní proteiny MeSH
• růstový faktor kmenových buněk MeSH
• thrombopoetin MeSH

In the work presented here, changes in haematopoiesis of mice (B6129SF2/J) were studied 1 year after their whole-body exposure to a dose of 7 Gy (72% of mice survived). The irradiated mice were compared with non-irradiated younger (4 months of age) and older (16 months of age) mice. There was a significant increase in the relative abundance of primitive stem cells with long-term capability of the haematopoiesis recovery lin(-)/Sca-1(+)/CD117(+)/CD34(-) in the bone marrow of mice aged 16 months (irradiated and non-irradiated) compared with those aged 4 months. In terms of the ability to respond to further whole-body irradiation at a dose of 1 Gy, the presence of γH2A.X foci was studied in lin(-) bone marrow cells. There was a considerable number of persisting foci in lin(-) stem cells isolated from the bone marrow of the older irradiated mice. In the blood count from the peripheral blood of the older mice (both non-irradiated and irradiated at 7 Gy), there was a significant increase in granulocytes. In the group exposed to 7 Gy, the numbers of thrombocytes significantly increased, and on the contrary, the numbers of erythrocytes, the amount of haemoglobin, and haematocrit significantly decreased.

• MeSH
• buněčné linie MeSH
• celotělové ozáření metody   MeSH
• erytrocyty metabolismus   účinky záření   MeSH
• granulocyty metabolismus   účinky záření   MeSH
• hematopoetické kmenové buňky cytologie   metabolismus   účinky záření   MeSH
• hematopoéza účinky záření   MeSH
• hemoglobiny metabolismus   účinky záření   MeSH
• histony metabolismus   MeSH
• kostní dřeň účinky záření   MeSH
• myši MeSH
• trombocyty metabolismus   účinky záření   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gamma-H2AX protein, mouse MeSH Prohlížeč
• hemoglobiny MeSH
• histony MeSH

Cell mobilization, a process that influences circulation, margination, and finally, homing play key roles in the regeneration processes mediated by stem cells. Recent studies as well as prior studies from our group indicate an important role of the spleen in hematopoietic reconstitution, but to date the role of the spleen in hematopoietic reconstitution has been unclear and it has not been precisely documented in ablated animals. Therefore, we undertook the present study to define more closely the role of the spleen in hematopoietic reconstitution in lethally irradiated mice. After transplantation of irradiated mice with lacZ+ -marked lin- / CD117+ bone marrow cells, we compared splenectomized mice (T(S), splenectomy performed prior to irradiation) to nonsplenectomized, irradiated mice (T(N)) as well as to normal (unirradiated) mice. Impaired hematopoietic reconstitution was observed in T(S) mice. Splenectomy markedly altered the distribution of hematopoietic stem cells, as demonstrated by fluorescence-activated cell sorting analysis of endogenous CD117+ cells in the thymus and bone marrow of recipients. Cell engraftment was demonstrated by histochemical and polymerase chain reaction analyses of recipient tissues. These experiments demonstrated that in T(S) animals, transplanted hematopoietic stem cells mobilized to extravascular tissues, particularly the gastrointestinal tract. The number of donor cells in recipient tissues continued to increase for 30 days after transplantation with the highest numbers observed in the T(S) group. DNA marking analysis led to the conclusion that engrafted cells were not only integrated into recipient tissues but were also capable of performing complex cellular processes, including proliferation and repair. Our results are consistent with the novel possibility that cellular repair markedly affects stem cell regenerative functions and that repair is markedly influenced by the integrity and presence of organs not directly involved in specific tissue regeneration processes, particularly the spleen.

• MeSH
• beta-galaktosidasa genetika   metabolismus   MeSH
• časové faktory MeSH
• exprese genu MeSH
• hematopoetické kmenové buňky cytologie   metabolismus   MeSH
• hematopoéza účinky záření   MeSH
• imunohistochemie MeSH
• kostní dřeň metabolismus   účinky záření   MeSH
• myši kmene 129 MeSH
• myši transgenní MeSH
• myši MeSH
• počet lymfocytů MeSH
• pohyb buněk * MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferační antigen buněčného jádra metabolismus   MeSH
• protoonkogenní proteiny c-kit metabolismus   MeSH
• průtoková cytometrie MeSH
• splenektomie metody   MeSH
• thymus cytologie   metabolismus   MeSH
• transplantace kostní dřeně MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-galaktosidasa MeSH
• proliferační antigen buněčného jádra MeSH
• protoonkogenní proteiny c-kit MeSH

Hematopoiesis-modulating action of meloxicam, a cyclooxyge-nase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally gamma-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated. Granulocyte/macrophage progenitor cells counts were used to monitor these effects. Meloxicam and exogenous G-CSF did not act synergistically when given in combination, but could be mutually substituted during their repeated administration. The results suggest a promising possibility of using meloxicam as an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression.

• MeSH
• buněčná diferenciace MeSH
• celotělové ozáření MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   krev   účinky léků   MeSH
• granulocyty cytologie   účinky léků   účinky záření   MeSH
• hematopoéza účinky léků   MeSH
• inhibitory cyklooxygenasy 2 farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• kostní dřeň účinky léků   účinky záření   MeSH
• lékové interakce MeSH
• leukopenie prevence a kontrola   MeSH
• meloxikam MeSH
• myši inbrední CBA MeSH
• myši MeSH
• thiaziny farmakologie   MeSH
• thiazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor stimulující kolonie granulocytů MeSH
• inhibitory cyklooxygenasy 2 MeSH
• meloxikam MeSH
• thiaziny MeSH
• thiazoly MeSH

Meloxicam, a selective inhibitor of cyclooxygenase 2, a nonsteroidal anti-inflammatory drug with an improved side-effects profile in terms of gastrointestinal toxicity, has been found to stimulate hematopoiesis in whole-body gamma-irradiated mice. A distinct corroboration of this positive action of meloxicam is an enhancement of the recovery of hematopoietic progenitor cells committed to granulocyte-macrophage and erythroid development, which has been demonstrated in sublethally irradiated animals treated with meloxicam at a dose of 20 mg/kg administered intraperitoneally either singly 1 h before irradiation or repeatedly after radiation exposure. The results suggest that meloxicam can be added to the list of biological response modifiers that can be used in the treatment of hematopoietic damage induced by ionizing radiation.

• MeSH
• celotělové ozáření škodlivé účinky   MeSH
• dávka záření MeSH
• hematopoéza účinky léků   účinky záření   MeSH
• inhibitory cyklooxygenasy 2 aplikace a dávkování   MeSH
• kostní dřeň účinky léků   zranění   patologie   účinky záření   MeSH
• kultivované buňky MeSH
• meloxikam MeSH
• myši MeSH
• radioprotektivní látky aplikace a dávkování   MeSH
• thiaziny aplikace a dávkování   MeSH
• thiazoly aplikace a dávkování   MeSH
• záření gama škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory cyklooxygenasy 2 MeSH
• meloxikam MeSH
• radioprotektivní látky MeSH
• thiaziny MeSH
• thiazoly MeSH