Single neonatal irradiation induces long-term gene expression changes in the thyroid gland, which may be involved in the tumorigenesis.

Exposure to ionizing radiation in childhood has been recognized as a risk factor for thyroid cancer. We previously demonstrated that neonatal X-irradiation induced specific deformation of the thyroid follicles. Here, we further analyzed this model to understand the possible relationship with thyroid carcinogenesis. Wistar rats were subjected to cervical X-irradiation at different ages of 1-8 weeks old and at different doses of 1.5-12 Gy. For tumor promotion, rats were fed with an iodine-deficient diet (IDD). In cervically X-irradiated neonatal rats, the size of thyroid follicles decreased, accompanied by an increase in the number of TUNEL-positive cells. Fas and Lgals3 mRNA levels increased, while Mct8 and Lat4 expressions decreased. The co-administration of IDD induced the proliferation and the upregulation in Lgals3 expression, resulting in thyroid adenoma development at 28 weeks post-exposure. Our data demonstrated that single neonatal X-irradiation induced continuous apoptotic activity in the thyroid with the long-term alternation in Fas, Mct8, Lat4, and Lgals3 mRNA expressions. Some of these changes were similar to those induced by IDD, suggesting that neonatal X-irradiation may partially act as a thyroid tumor promoter. These radiation-induced thyroidal changes may be enhanced by the combined treatment with IDD, resulting in the early development of thyroid adenoma.

Comparison of methods to experimentally induce opacification and elasticity change in ex vivo porcine lenses.

At the moment, cataract, which is the opacification of the eye's lens, can only be treated by surgery. In order to develop and test new pharmacological treatment strategies for the disease, there is a need for an appropriate in vitro model using ex vivo animal lenses. In this study, porcine lenses were incubated in either culture medium, glucose, triamcinolone acetonide, sodium chloride, hydrogen peroxide, sodium selenite, neutral buffered formalin, or were exposed to microwave heating to experimentally induce lens opacification. Changes in the lens morphology, weight, size, and elasticity were monitored 7 days after treatment. The fastest induction of dense opacification was seen in lenses exposed to sodium chloride, neutral buffered formalin, and microwave heating. No change in the size and weight of the lenses were detected, whereas loss in elasticity could be detected in lenses treated with formalin solution or microwave heating. Thus, neutral buffered formalin- and microwave-treated ex vivo porcine lenses seem to be a suitable model for mature cataracts, whereas hypertonic sodium chloride may be useful for studies on osmolarity-induced lens opacification.

Efficacy and efficiency of Green-Light XPS 180-watt laser system for benign prostatic enlargement in patients treated with 5α-reductase inhibitors.

OBJECTIVE: Aim of the study was to evaluate efficacy and efficiency of 180-watt Green-Light XPS (GL-XPS) laser photoselective vaporization of the prostate (PVP) in patients under 5-Alpha-Reductase Inhibitors (5ARI) treatment. PATIENTS AND METHODS: A consecutive series of patients with lower urinary tract symptoms due to benign prostatic enlargement treated by PVP with the GL-XPS were enrolled. Patients were divided in two groups according to the chronic use (>6 months) of 5ARI. These two groups were compared on lasing density (kilojoules per prostate volume), vaporization efficiency (prostate volume per lasing time), vaporization power (kilojoules per lasing time), Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement. Follow-up was performed at 3, 6 and 12 months with International Prostate Symptom Score, Uroflowmetry parameters and PSA. RESULTS: Overall 193 patients were enrolled. Out of them 87/193 (45%) were on 5ARI treatment. No significant differences were recorded between the two groups at baseline. Median age was 68 years old and median prostate volume was 60 ml. In terms of laser efficiency, no statistically significant differences were recorded in terms of lasing time (25 min vs. 24.5 min; p>0.05); energy used (250 kJ vs. 221 kJ; p>0.05), lasing density (6.8 kJ/ml vs. 6.6 kJ/ml, p>0.05), vaporization efficiency (1.4 ml/min vs. 1.3 ml/min, p>0.05) and vaporization power (9.6 kJ/min vs. 9.4 kJ/min; p>0.05). Finally, no significant differences were also recorded postoperatively in the two groups in terms of PSA reduction, improvement in symptom score and uroflowmetry parameters (p>0.05). CONCLUSIONS: Thirty-seven efficacy and efficiency outcomes were not statistically different between the two groups. 5ARI does not reduce the performance and ability of the 180-watt Green-Light XPS laser system.

Local application of low level laser therapy in mice ameliorates ovarian damage induced by cyclophosphamide.

The aim of the present study is to assess whether low level laser therapy (LLLT) can protect ovaries from chemotherapy-induced gonadotoxicity using a mice model of premature ovarian failure induced by cyclophosphamide (CTX). LLLT (64 J/cm2) increased the number of antral follicles whilst decreasing the number of atretic follicles compared to CTX alone. LLLT increased the number of primordial follicles compared with those in the CTX group but they did not differ from those in the control group. LLLT treatment increased the number of AMH-positive follicles compared to CTX alone. LLLT application increased ovarian weight, serum progesterone concentration and P450scc protein levels compared to CTX alone. LLLT reduced the apoptosis in antral follicles and the BAX/BCL-2 ratio compared to CTX alone. Vascular morphology, analysed by CD31 and α-SMA immunostaining, was restored in LLLT-treated ovaries compared to CTX alone. In conclusion, application of LLLT prior to CTX might serve as a promising and novel protocol to preserve female fertility in cancer survivors.

Noninvasive Assessment of Neurodevelopmental Disorders after In Utero Irradiation in Mice: An In Vivo Anatomical and Diffusion MRI Study.

In utero exposure to ionizing radiation can lead to cerebral alterations during adulthood. Using anatomical magnetic resonance imaging (MRI), it is possible to assess radiation-induced structural brain damage noninvasively. However, little is currently known about microstructure alterations in brain tissue. Therefore, the goal of this study was to establish, based on an original and robust pipeline of MRI image analysis, whether the long-term effects of in utero radiation exposure on brain tissue microstructure could be detected noninvasively. Pregnant C57BL/6N mice received a single dose of 1 Gy on gestation day 14.5, which led to behavioral impairments in adults. At 3 months old, in vivo MRI data were acquired from in utero irradiated and nonirradiated male mice. An MRI protocol was designed to assess the effects of radiation on the parameters of brain volume, non-Gaussian diffusion (ADC0, kurtosis and signature index) and anisotropic diffusion (fractional anisotropy and mean, axial, radial diffusivities and anisotropic signature index) in 10 key cerebral structures defined using an in-house atlas of the mouse brain. Based on the relative amplitude of these anatomical and microstructural changes, maps of the radiosensitivity of the brain to in utero irradiation were created. We observed microcephaly in irradiated mice with noticeably larger volume changes in the cortex and the corpus callosum. We also observed significantly lower ADC0, anisotropy fraction (sFA), radial diffusivity (sRD), as well as signature index (S-index and SI3) values, which are original markers sensitive to tissue microstructure alterations. All these changes together are in favor of a decreased cellular "imprint" and in some regions a reduced density in myelinated axons. A reduction in the number and complexity of myelinated axons was further revealed by myelin basic protein immunostaining. Combining anatomical and diffusion MRI is a promising approach to noninvasively investigate the radiosensitivity of local brain areas in adult mice after in utero irradiation in terms of microstructure.

A longitudinal, randomized experimental pilot study to investigate the effects of airborne ultrasound on human mental health, cognition, and brain structure.

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants' bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

Phenotypic Study of Photomorphogenesis in Arabidopsis Seedlings.

Light is one of the most important environmental factors, serving as the energy source of photosynthesis and a cue for plant developmental programs, called photomorphogenesis. Here, we provide a standardized operation to measure physiological parameters of photomorphogenesis, including in hypocotyl length, cotyledon size, and anthocyanin content.

Effect of fractionated whole-brain irradiation on brain and plasma in a rat model: Metabolic, volumetric and histopathological changes.

In the present study, we investigated the correlation between histopathological, metabolic, and volumetric changes in the brain and plasma under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 32 Gy delivered in 4 fractions (dose 8 Gy per fraction) once a week on the same day for 4 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS) and imaging were used to detect metabolic and volumetric changes in the brain and plasma. Histopathological changes in the brain were determined by image analysis of immunofluorescent stained sections. Metabolic changes in the brain measured by 1H MRS before, 48 h, and 9 weeks after the end of fWBI showed a significant decrease in the ratio of total N-acetylaspartate to total creatine (tNAA/tCr) in the corpus striatum. We found a significant decrease in glutamine + glutamate/tCr (Glx/tCr) and, conversely, an increase in gamma-aminobutyric acid to tCr (GABA/tCr) in olfactory bulb (OB). The ratio of astrocyte marker myoinositol/tCr (mIns/tCr) significantly increased in almost all evaluated areas. Magnetic resonance imaging (MRI)-based brain volumetry showed a significant increase in volume, and a concomitant increase in the T2 relaxation time of the hippocampus. Proton nuclear magnetic resonance (1H NMR) plasma metabolomics displayed a significant decrease in the level of glucose and glycolytic intermediates and an increase in ketone bodies. The histomorphological analysis showed a decrease to elimination of neuroblasts, increased astrocyte proliferation, and a mild microglia response. The results of the study clearly reflect early subacute changes 9-11 weeks after fWBI with strong manifestations of brain edema, astrogliosis, and ongoing ketosis.

Capacity of proton beams in preserving normal liver tissue during proton beam therapy for hepatocellular carcinoma.

Unirradiated liver volume (ULV) preservation rate is an important factor associated with radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) undergoing proton beam therapy (PBT). The purpose of this study is to identify the predictors for ULV preservation and quantify the capacity of proton beams in normal liver sparing during PBT. We reviewed planning data of 92 patients with single intrahepatic HCC tumors undergoing PBT. The potential clinical and planning factors that may affect ULV preservation were involved in multiple linear regression for ULV preservation rate. The significant factors were determined to be predictors and their influences were quantified. The median ULV preservation rate was 62.08%. All the assessed clinical factors showed significant effects on ULV preservation rate: clinical target volume (CTV), P < 0.001; portal vein tumor thrombosis (PVTT), P = 0.010; left lobe tumor, P = 0.010. In contrast, none of the planning factors demonstrated significance. The coefficients of significant factors in multiple linear regression were 60.85 for intercept, -0.02 for CTV, -9.01 for PVTT and 8.31 for left lobe tumors. The capacity of proton beams to spare normal liver tissue during PBT for HCC is mainly affected by clinical factors. The baseline of the ULV preservation rate is 60.85%, decreasing 0.02% with each milliliter of CTV increase and 9.01% for tumors with PVTT, and increasing 8.31% for tumors limited to the left lobe. Further clinical studies should be carried out to correlate our dosimetric findings with clinical outcomes.

Irradiation dose does not affect male reproductive organ size, sperm storage, and female remating propensity in Ceratitis capitata.

The Mediterranean fruit fly Ceratitis capitata is a globally invasive pest, often controlled with the sterile insect technique (SIT). For the SIT, mass-rearing of the target insect followed by irradiation are imperatives. Sterile males are often less able to inhibit female remating and transfer less number of sperm, and even irradiation could affect male reproductive organs, with consequences for their ability to inhibit female remating. On the other hand, male age could affect their ability to modulate female response after mating. Here, we evaluated the quality of the genetic sexing strain Vienna-8-tsl mass-reared in Bioplanta San Juan, Argentina, under laboratory conditions, with regard to: (i) the ability of sterile males irradiated at 100 or 140 Gy to inhibit female remating, in the same day and at 24 h of first copulation; (ii) the ability of 3, 4 or 5 day-old sterile males to inhibit female remating at 24 h of first copulation, and (iii) the effect of a reduction in irradiation doses on the number of sperm stored by females and reproductive organ size in virgin males. Sterile males were better able than wild males to inhibit female remating in the same day of first copulation and as able as wild males 1 day after first copulation. Male age did not affect their ability to inhibit female receptivity. Number of sperm stored by females, testes size and ectodermal accessory glands size were not affected by male identity, while sterile 100 Gy males had larger mesodermal accessory glands than control lab males. A reduction in irradiation dose does not impact any variable measured, except for percentage of sperm-depleted females: females mated with sterile 100 Gy males had lower probabilities to store sperm. The results showed here are very encouraging for tsl Vienna 8 strain reared in Argentina and are discussed in comparison with previous studies in C. capitata female remating with dissimilar results.

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model.

BACKGROUND/AIM: The importance of hadron therapy in the cancer management is growing. We aimed to refine the biological effect detection using a vertebrate model. MATERIALS AND METHODS: Embryos at 24 and 72 h postfertilization were irradiated at the entrance plateau and the mid spread-out Bragg peak of a 150 MeV proton beam and with reference photons. Radiation-induced DNA double-strand breaks (DSB) and histopathological changes of the eye, muscles and brain were evaluated; deterioration of specific organs (eye, yolk sac, body) was measured. RESULTS: More and longer-lasting DSBs occurred in eye and muscle cells due to proton versus photon beams, albeit in different numbers. Edema, necrosis and tissue disorganization, (especially in the eye) were observed. Dose-dependent morphological deteriorations were detected at ≥10 Gy dose levels, with relative biological effectiveness between 0.99±0.07 (length) and 1.12±0.19 (eye). CONCLUSION: Quantitative assessment of radiation induced changes in zebrafish embryos proved to be beneficial for the radiobiological characterization of proton beams.

Effect of Heavy Ion 12C6+ Radiation on Lipid Constitution in the Rat Brain.

Heavy ions refer to charged particles with a mass greater than four (i.e., alpha particles). The heavy ion irradiation used in radiotherapy or that astronauts suffer in space flight missions induces toxicity in normal tissue and leads to short-term and long-term damage in both the structure and function of the brain. However, the underlying molecular alterations caused by heavy ion radiation have yet to be completely elucidated. Herein, untargeted and targeted lipidomic profiling of the whole brain tissue and blood plasma 7 days after the administration of the 15 Gy (260 MeV, low linear energy (LET) = 13.9 KeV/µm) plateau irradiation of disposable 12C6+ heavy ions on the whole heads of rats was explored to study the lipid damage induced by heavy ion radiation in the rat brain using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) technology. Combined with multivariate variables and univariate data analysis methods, our results indicated that an orthogonal partial least squares discriminant analysis (OPLS-DA) could clearly distinguish lipid metabolites between the irradiated and control groups. Through the combination of variable weight value (VIP), variation multiple (FC), and differential (p) analyses, the significant differential lipids diacylglycerols (DAGs) were screened out. Further quantitative targeted lipidomic analyses of these DAGs in the rat brain tissue and plasma supported the notion that DAG 47:1 could be used as a potential biomarker to study brain injury induced by heavy ion irradiation.

The effect of chronic low-dose environmental radiation on organ mass of bank voles in the Chernobyl exclusion zone.

PURPOSE: Animals are exposed to environmental ionizing radiation (IR) externally through proximity to contaminated soil and internally through ingestion and inhalation of radionuclides. Internal organs can respond to radioactive contamination through physiological stress. Chronic stress can compromise the size of physiologically active organs, but studies on wild mammal populations are scarce. The effects of environmental IR contamination on organ masses were studied by using a wild rodent inhabiting the Chernobyl exclusion zone (CEZ). MATERIAL AND METHODS: The masses of brain, heart, kidney, spleen, liver and lung were assessed from bank voles (Myodes glareolus) captured from areas across radioactive contamination gradient within the CEZ. Relative organ masses were used to correct for the body mass of an individual. RESULTS: Results showed a significant negative correlation between IR level in the environment and relative brain and kidney mass. A significant positive correlation between IR and relative heart mass was also found. Principal component analysis (PCA) also suggested positive relationship between IR and relative spleen mass; however, this relationship was not significant when spleen was analyzed separately. There was no apparent relationship between IR and relative liver or lung mass. CONCLUSIONS: Results suggest that in the wild populations even low but chronic doses of IR can lead to changes in relative organ mass. The novelty of these result is showing that exposure to low doses can affect the organ masses in similar fashion as previously shown on high, acute, radiation doses. These data support the hypothesis that wildlife might be more sensitive to IR than animals used in laboratory studies. However, more research is needed to rule out the other indirect effects such as radiosensitivity of the food sources or possible combined stress effects from e.g. infections.

Long-term Effects of Radioiodine in Toxic Multinodular Goiter: Thyroid Volume, Function, and Autoimmunity.

CONTEXT: Long-term studies evaluating the treatment of toxic multinodular goiter (TMNG) with fixed activities of radioiodine (RAI) are lacking. OBJECTIVE: The objective of this work is to describe the effects of 15 mCi on thyroid volume, function, and autoimmunity in the long term. DESIGN AND SETTING: A population-based, retrospective analysis with up to 12 years of follow-up was conducted in Siena, Italy. PARTICIPANTS: Adult patients (n = 153) with TMNG, naive to RAI, were included. METHODS: Evaluation was performed of thyroid function, antithyroid antibodies, and ultrasound scans before and yearly after RAI. MAIN OUTCOME MEASURES: Evaluations included hyperthyroidism cure, hypothyroidism, volume reduction, nadir and regain, and antibody titer change. RESULTS: The study revealed mean volume reductions greater than or equal to 50% at 3 years after RAI; the greatest annual reduction was observed during the first year (30 ± 17.8%; P < .001). Most patients (60%) achieved their volume nadir 3 to 6 years after RAI. Although 22% patients showed volume regain, the net reduction was statistically significant as late as 9 years after RAI (P = .005). The mean time to hypothyroidism was 2.7 ± 2.4 years, and it was associated with greater reductions in volume (P = .01). During the first 3 years after treatment, hyperthyroid patients decreased approximately by 50% per year without additional RAI. There was no statistically significant association of antibody titers with thyroid function except for antithyrotropin receptor antibodies and hyperthyroidism (P = .004). At the end of follow-up there were 61.6% euthyroid patients, 11% hyperthyroid (4.8% overt), and 27.4% hypothyroid patients (2.7% overt). Hyperthyroidism was cured in 89%. CONCLUSIONS: The treatment of TMNG with 15 mCi of RAI induced low hypothyroidism rates while providing high cure rates and significant volume reduction, which was maintained in the long term.

Estimating brain volume loss after radiation therapy in children treated for posterior fossa tumors (Corpus callosum and whole brain volume changes following radiotherapy in children).

BACKGROUND: More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT). OBJECTIVES: The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique. MATERIAL AND METHODS: Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (<30 Gy, Group 2, n = 9) and high-dose whole-brain RT (>30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted. RESULTS: Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements. CONCLUSIONS: The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT.

Decreased Tongue Volume Post Radiation.

OBJECTIVES: To evaluate volume changes within the tongue post chemoradiation therapy (CRT). STUDY DESIGN: Retrospective review. SETTING: Academic Medical Center. SUBJECTS AND METHODS: Subjects included 19 patients that received CRT as the primary treatment for tonsillar or hypopharynx squamous cell carcinoma. Tongue volumes were calculated by three raters from thin slice computed tomography images collected before treatment and up to 29 months post-CRT. Body mass index (BMI) was also collected at each time point. RESULTS: Inter-rater reliability was high with an ICC of 0.849 (95% CI = 0.773, 0.905). Linear mixed effects modeling showed a mean decrease of 0.45 cm3 (standard error of the mean [SEM] = 0.11) in tongue volume per month post-CRT (P < .001). However, the addition of BMI to the model was significant (χ2 (4) = 25.0, P < .001), indicating that BMI was a strong predictor of tongue volume, with a mean decrease of 1.75 cm3 (SEM = 0.49) in tongue volume per unit decrease in BMI (P < .001) and reducing the post-CRT effect on tongue volume decrease per month to 0.23 cm3 (P = .02). BMI significantly (P < .001) decreased by 0.11 units (SEM = 0.02) per month post radiation. CONCLUSION: Tongue dysfunction and decreased tongue strength are significant contributors to the dysphagia that patients experience after receiving CRT. In this study, both tongue volume and BMI decreased post-CRT; therefore, BMI could potentially be used as a predictor of tongue volume post-CRT.

Effect of lung volume on helical radiotherapy in esophageal cancer: are there predictive factors to achieve acceptable lung doses?

PURPOSE: The dose received by the lungs in radiotherapy (RT) is affected by the patient's current lung volume. The presence of predictive factors and cut-off points were investigated to achieve acceptable lung doses in esophageal cancer (EC) treatment. METHODS: Virtual RT volumes of supracarinal EC were delineated. RT plans were designed with standard criteria in the TomoTherapy planning system (TomoTherapy Inc., Madison, WI, USA). The total dose was 50.4 Gy (1.8 Gy/fraction). ROC (Receiver operating characteristic) analysis and Mann-Whitney U tests were performed. RESULTS: There was a total of 65 patient plans included. ROC analysis showed that lung/PTV (Planning target volume) volume ratio (AUC [Area under curve]: 0.91, 95% CI: 0.83-0.99, p = 0.000) and bilateral lung volume (AUC: 0.81, 95% CI: 0.70-0.92, p = 0.000) have diagnostic power to predict the suitability of RT plans according to QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) for lung dose constraints. The cut-off points of 7 and 3500 cc were selected for lung/PTV ratio and bilateral lung volume, respectively. The effect of the cut-off points on the dose data was assessed with the Mann-Whitney U test. The mean lung and heart doses, lung V5, V15, and V20, as well as heart V5, V20, V30, and V45 values were found to be lower in both groups separated by cut-off points (p < 0.05). CONCLUSION: The lung/PTV ratio ≥7 and bilateral lung volume ≥3500 cc cut-off points are predictive of whether TomoTherapy plans may meet QUANTEC lung dose limits in patients with supracarinal esophageal cancer. The patients with lung/PTV ratio and lung volume above these cut-off points may be candidates for treatment with TomoTherapy.

177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Dose Response in Small Intestinal Neuroendocrine Tumors.

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs). OBJECTIVE: To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage. MATERIALS AND METHODS: Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response. RESULTS: At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4-326.9) and 140 Gy (range 50.9-487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01). CONCLUSIONS: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.

Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects.

Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.

Effects of the combination of low-level laser therapy and anionic polymer membranes on bone repair.

In view of the limitations of bone reconstruction surgeries using autologous grafts as a gold standard, tissue engineering is emerging as an alternative, which permits the fabrication and improvement of scaffolds to stimulate osteogenesis and angiogenesis, processes that are essential for bone repair. Polymers are used to mimic the extracellular bone matrix and support cell growth. In addition, bone neoformation can be induced by external factors such as laser irradiation, which stimulates bone metabolism. The objective of this study was to evaluate the regeneration of bone defects using collagen and elastin membranes derived from intestinal serosa and bovine auricular cartilage combined with low-level laser application. Thirty-six Wistar rats were operated to create a 3-mm defect in the distal metaphysis of the left femur and divided into six groups: G1 (control, no treatment); G2 (laser); G3 (elastin graft), G4 (elastin+laser); G5 (collagen graft); G6 (collagen+laser). The animals were sacrificed 6 weeks after surgery and the femurs were removed for analysis of bone repair. Macroscopic and radiological results showed the absence of an infectious process in the surgical area. This was confirmed by histological analysis, which revealed no inflammatory infiltrate. Histomorphometry showed that the formation of new bone started from the margins of the bone defect and its volume was greater in elastin+laser and collagen+laser. We conclude that newly formed bone in the graft area was higher in the groups that received the biomaterials and laser. The collagen and elastin matrices showed biocompatibility.