Modulation of growth by aromatase inhibitor treatment in boys: Efficacy and safety

Without estrogen action, the fusion of the growth plates is postponed and statural growth continues for an exceptionally long time. Aromatase inhibitors, blockers of estrogen biosynthesis, have therefore emerged as a new potential option for the treatment of children with short stature. We investigated the efficacy of the aromatase inhibitor letrozole in the treatment of boys with idiopathic short stature (ISS) using a randomised, placebo-controlled, double-blind research setting. A total of 30 boys completed the two-year treatment. By decreasing estrogen-mediated central negative feedback, letrozole increased gonadotrophin and testosterone secretion in pubertal boys, whereas the pubertal increase in IGF-I was inhibited. Treatment with letrozole effectively delayed bone maturation and increased predicted adult height by 5.9 cm (P0.001), while placebo had no effect on either parameter. The effect of letrozole treatment on near-final height was studied in another population, in boys with constitutional delay of puberty, who received letrozole (n=9) or placebo (n=8) for one year, in combination with low-dose testosterone for six months during adolescence. The mean near-final height of boys randomised to receive testosterone and letrozole was significantly greater than that of boys who received testosterone and placebo (175.8 vs. 169.1 cm, P=0.04). As regards safety, treatment effects on bone health, lipid metabolism, insulin sensitivity, and body composition were monitored in boys with ISS. During treatment, no differences in bone mass accrual were evident between the treatment groups, as evaluated by dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck. Bone turnover and cortical bone growth, however, were affected by letrozole treatment. As indicated by differences in markers of bone resorption (U-INTP) and formation (S-PINP and S-ALP), the long-term rate of bone turnover was lower in letrozole-treated boys, despite their more rapid advancement in puberty. Letrozole stimulated cortical bone growth in those who progressed in puberty: the metacarpal index (MCI), a measure of cortical bone thickness, increased more in letrozole-treated pubertal boys than in placebo-treated pubertal boys (25% vs. 9%, P=0.007). The change in MCI correlated positively with the mean testosterone-to-estradiol ratio. In post-treatment radiographic evaluation of the spine, a high rate of vertebral deformities - mild anterior wedging and mild compression deformities - were found in both placebo and letrozole groups. In pubertal boys with ISS treated with letrozole, stimulated testosterone secretion was associated with a decrease in the percentage of fat mass and in HDL-cholesterol, while LDL-cholesterol and triglycerides remained unchanged. Insulin sensitivity, as evaluated by HOMA-IR, was not significantly affected by the treatment. In summary, treatment with the aromatase inhibitor letrozole effectively delayed bone maturation and increased predicted adult height in boys with ISS. Long-term follow-up data of boys with constitutional delay of puberty, treated with letrozole for one year during adolescence, suggest that the achieved gain in predicted adult height also results in increased adult height. However, until the safety of aromatase inhibitor treatment in children and adolescents is confirmed, such treatment should be considered experimental.

Craving mediates stress in predicting lapse during alcohol dependence treatment

Background Stress, craving, and depressed mood have all been implicated in alcohol use treatment lapses. Few studies have examined all 3 factors. Progress has been limited because of difficulties with craving assessment. The Alcohol Craving Experience Questionnaire (ACE) is a new measure of alcohol craving. It is both psychometrically sound and conceptually rigorous. This prospective study examines a stress–treatment response model that incorporates mediation by craving and moderation by depressed mood and pharmacotherapy. Methods Five hundred and thirty-nine consecutively treated alcohol-dependent patients voluntarily participated in an abstinence-based 12-week cognitive-behavioral therapy (CBT) program at a hospital alcohol and drug outpatient clinic. Measures of stress, craving, depressed mood, and alcohol dependence severity were administered prior to treatment. Treatment lapse and treatment dropout were assessed over the 12-week program duration. Results Patients reporting greater stress experienced stronger and more frequent cravings. Stronger alcohol craving predicted lapse, after controlling for dependence severity, stress, depression, and pharmacotherapy. Alcohol craving mediated stress to predict lapse. Depressed mood and anticraving medication were not significant moderators. Conclusions Among treatment seeking, alcohol-dependent patients, craving mediated the relationship between stress and lapse. The effect was not moderated by depressed mood or anticraving medication.

12-weeks supervised exercise training is a feasible and efficacious treatment for reducing depression in youth with major depressive disorder

Introduction: Major Depressive Disorder (MDD) has high prevalence among adolescents and young adults. Evidence of any effective treatments is limited. Exercise as an effective treatment for adults has some support but studies in younger populations are lacking. Therefore the aim of this study was to investigate the feasibility and preliminary efficacy of brief motivational interviewing (MI) plus 12-weeks exercise training as a treatment for MDD in youth...

The use of circular surface aerators in wastewater treatment tanks

Aeration experiments were conducted in different sized baffled and unbaffled circular surface aeration tanks to study their relative performance on oxygen transfer process while aerating the same volume of water. Experiments were carried out with the objective of ascertaining the effect of baffle on oxygen transfer coefficient k. Simulation equations govern the oxygen transfer coefficient with the theoretical power per unit volume, X and actual power per unit volume, P-V. It has been found that, for any given X, circular tanks with baffle produce higher values of k than unbaffled circular tanks, but in terms of actual power consumption unbaffled tanks consume less power when compared to baffled circular tanks to achieve the same value of k. It has been found that in terms of energy consumption, epsilon, baffled tanks consume more energy than unbaffled tanks at any value of X. This suggests that the unbaffled circular tank gives a better performance as far as energy consumption is concerned and hence better economy. An example illustrating the energy conservation to aerate the same volume of water in both types of aerators is given. (c) 2007 Society of Chemical Industry.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: Results of an open-label, randomized, controlled phase II study (CERTO)

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. Results: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator. Conclusions: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.

Micro-treatment options for components of organic fraction of MSW in residential areas

There is a growing interest in management of MSW through micro-treatment of organic fraction of municipal solid wastes (OFMSW) in many cities of India. The OFMSW fraction is high (> 80%) in many pockets within South Indian cities like Bangalore, Chikkamagalur, etc. and is largely represented by vegetable, fruit, packing and garden wastes. Among these, the last three have shown problems for easy decomposition. Fruit wastes are characterized by a large pectin supported fraction that decomposes quickly to organic acids (becomes pulpy) that eventually slow down anaerobic and aerobic decomposition processes. Paper fraction (newsprint and photocopying paper) as well as paddy straw (packing), bagasse (from cane juice stalls) and tree leaf litter (typical garden waste and street sweepings) are found in reasonably large proportions in MSW. These decompose slowly due to poor nutrients or physical state. We have examined the suitability of these substrates for micro-composting in plastic bins by tracking decomposition pattern and physical changes. It was found that fruit wastes decompose rapidly to produce organic acids and large leachate fraction such that it may need to be mixed with leachate absorbing materials (dry wastes) for good composting. Leaf litter, paddy straw and bagasse decompose to the tune of 90, 68 and 60% VS and are suitable for composting micro-treatment. Paper fractions even when augmented with 10% leaf compost failed to show appreciable decomposition in 50 days. All these feedstocks were found to have good biological methane potential (BMP) and showed promise for conversion to biogas under a mixed feed operation. Suitability of this approach was verified by operating a plug-flow type anaerobic digester where only leaf litter gathered nearby (as street sweepings) was used as feedstock. Here only a third of the BMP was realized at this scale (0.18 m(3) biogas/kg VS 0.55 m(3)/kg in BMP). We conclude that anaerobic digestion in plug-flow like digesters appear a more suitable micro-treatment option (2-10 kg VS/day) because in addition to compost it also produces biogas for domestic use nearby.

Humanitaarisuuden varjossa : Poliittiset tekijät lastensiirroissa Ruotsiin sotiemme aikana ja niiden jälkeen

The evacuation of Finnish children to Sweden during WW II has often been called a small migration . Historical research on this subject is scarce, considering the great number of children involved. The present research has applied, apart from the traditional archive research, the framework of history-culture developed by Rüsen in order to have an all-inclusive approach to the impact of this historical event. The framework has three dimensions: political, aesthetic and cognitive. The collective memory of war children has also been discussed. The research looks for political factors involved in the evacuations during the Winter War and the Continuation War and the post-war period. The approach is wider than a purely humanitarian one. Political factors have had an impact in both Finland and Sweden, beginning from the decision-making process and ending with the discussion of the unexpected consequences of the evacuations in the Finnish Parliament in 1950. The Winter War (30.11.1939 13.3.1940) witnessed the first child transports. These were also the model for future decision making. The transports were begun on the initiative of Swedes Maja Sandler, the wife of the resigned minister of foreign affairs Rickard Sandler, and Hanna Rydh-Munck af Rosenschöld , but this activity was soon accepted by the Swedish government because the humanitarian help in the form of child transports lightened the political burden of Prime Minister Hansson, who was not willing to help Finland militarily. It was help that Finland never asked for and it was rejected at the beginning. The negative response of Minister Juho Koivisto was not taken very seriously. The political forces in Finland supporting child transports were stronger than those rejecting them. The major politicians in support belonged to Finland´s Swedish minority. In addition, close to 1 000 Finnish children remained in Sweden after the Winter War. No analysis was made of the reasons why these children did not return home. A committee set up to help Finland and Norway was established in Sweden in 1941. Its chairman was Torsten Nothin, an influential Swedish politician. In December 1941 he appealed to the Swedish government to provide help to Finnish children under the authority of The International Red Cross. This plea had no results. The delivery of great amounts of food to Finland, which was now at war with Great Britain, had automatically caused reactions among the allies against the Swedish imports through Gothenburg. This included the import of oil, which was essential for the Swedish navy and air force. Oil was later used successfully to force a reduction in commerce between Sweden and Finland. The contradiction between Sweden´s essential political interests and humanitarian help was solved in a way that did not harm the country´s vital political interests. Instead of delivering help to Finland, Finnish children were transported to Sweden through the organisations that had already been created. At the beginning of the Continuation War (25.6.1941 27.4.1945) negative opinion regarding child transports re-emerged in Finland. Karl-August Fagerholm implemented the transports in September 1941. In 1942, members of the conservative parties in the Finnish Parliament expressed their fear of losing the children to the Swedes. They suggested that Finland should withdraw from the inter-Nordic agreement, according to which the adoptions were approved by the court of the country where the child resided. This initiative failed. Paavo Virkkunen, an influential member of the conservative party Kokoomus in Finland, favoured the so-called good-father system, where help was delivered to Finland in the form of money and goods. Virkkunen was concerned about the consequences of a long stay in a Swedish family. The risk of losing the children was clear. The extreme conservative party (IKL, the Patriotic Movement of the Finnish People) wanted to alienate Finland from Sweden and bring Finland closer to Germany. Von Blücher, the German ambassador to Finland, had in his report to Berlin, mentioned the political consequences of the child transports. Among other things, they would bring Finland and Sweden closer to each other. He had also paid attention to the Nordic political orientation in Finland. He did not question or criticize the child transports. His main interest was to increase German political influence in Finland, and the Nordic political orientation was an obstacle. Fagerholm was politically ill-favoured by the Germans, because he had a strong Nordic political disposition and had criticised Germany´s activities in Norway. The criticism of child transports was at the same time criticism of Fagerholm. The official censorship organ of the Finnish government (VTL) denied the criticism of child transports in January 1942. The reasons were political. Statements made by members of the Finnish Parliament were also censored, because it was thought that they would offend the Swedes. In addition, the censorship organ used child transports as a means of active propaganda aimed at improving the relations between the two countries. The Finnish Parliament was informed in 1948 that about 15 000 Finnish children still remained in Sweden. These children would stay there permanently. In 1950 the members of the Agrarian Party in Finland stated that Finland should actively strive to get the children back. The party on the left (SKDL, the Democratic Movement of Finnish People) also focused on the unexpected consequences of the child transports. The Social Democrats, and largely Fagerholm, had been the main force in Finland behind the child transports. Members of the SKDL, controlled by Finland´s Communist Party, stated that the war time authorities were responsible for this war loss. Many of the Finnish parents could not get their children back despite repeated requests. The discussion of the problem became political, for example von Born, a member of the Swedish minority party RKP, related this problem to foreign policy by stating that the request to repatriate the Finnish children would have negative political consequences for the relations between Finland and Sweden. He emphasized expressing feelings of gratitude to the Swedes. After the war a new foreign policy was established by Prime Minister (1944 1946) and later President (1946 1956) Juho Kusti Paasikivi. The main cornerstone of this policy was to establish good relations with the Soviet Union. The other, often forgotten, cornerstone was to simultaneously establish good relations with other Nordic countries, especially Sweden, as a counterbalance. The unexpected results of the child evacuation, a Swedish initiative, had violated the good relations with Sweden. The motives of the Democratic Movement of Finnish People were much the same as those of the Patriotic Movement of Finnish People. Only the ideology was different. The Nordic political orientation was an obstacle to both parties. The position of the Democratic Movement of Finnish People was much better than that of the Patriotic Movement of Finnish People, because now one could clearly see the unexpected results, which included human tragedy for the many families who could not be re-united with their children despite their repeated requests. The Swedes questioned the figure given to the Finnish Parliament regarding the number of children permanently remaining in Sweden. This research agrees with the Swedes. In a calculation based on Swedish population registers, the number of these children is about 7 100. The reliability of this figure is increased by the fact that the child allowance programme began in Sweden in 1948. The prerequisite to have this allowance was that the child be in the Swedish population register. It was not necessary for the child to have Swedish nationality. The Finnish Parliament had false information about the number of Finnish children who remained in Sweden in 1942 and in 1950. There was no parliamentary control in Finland regarding child transports, because the decision was made by one cabinet member and speeches by MPs in the Finnish Parliament were censored, like all criticism regarding child transports to Sweden. In Great Britain parliamentary control worked better throughout the whole war, because the speeches regarding evacuation were not censored. At the beginning of the war certain members of the British Labour Party and the Welsh Nationalists were particularly outspoken about the scheme. Fagerholm does not discuss to any great extent the child transports in his memoirs. He does not evaluate the process and results as a whole. This research provides some possibilities for an evaluation of this sort. The Swedish medical reports give a clear picture of the physical condition of the Finnish children when arriving in Sweden. The transports actually revealed how bad the situation of the poorest children was. According to Titmuss, similar observations were made in Great Britain during the British evacuations. The child transports saved the lives of approximately 2 900 children. Most of these children were removed to Sweden to receive treatment for illnesses, but many among the healthy children were undernourished and some suffered from the effects of tuberculosis. The medical inspection in Finland was not thorough. If you compare the figure of 2 900 children saved and returned with the figure of about 7 100 children who remained permanently in Sweden, you may draw the conclusion that Finland as a country failed to benefit from the child transports, and that the whole operation was a political mistake with far-reaching consequenses. The basic goal of the operation was to save lives and have all the children return to Finland after the war. The difficulties with the repatriation of the children were mainly psychological. The level of child psychology in Finland at that time was low. One may question the report by Professor Martti Kaila regarding the adaptation of children to their families back in Finland. Anna Freud´s warnings concerning the difficulties that arise when child evacuees return are also valid in Finland. Freud viewed the emotional life of children in a way different from Kaila: the physical survival of a small child forces her to create strong emotional ties to the person who is looking after her. This, a characteristic of all small children, occurred with the Finnish children too, and it was something the political decision makers in Finland could not see during and after the war. It is a characteristic of all little children. Yet, such experiences were already evident during the Winter War. The best possible solution had been to limit the child transports only to children in need of medical treatment. Children from large and poor families had been helped by organising meals and by buying food from Denmark with Swedish money. Assisting Finland by all possible means should have been the basic goal of Fagerholm in September 1941, when the offer of child transports came from Sweden. Fagerholm felt gratitude towards the Swedes. The risks became clear to him only in 1943. The war children are today a rather scattered and diffuse group of people. Emotionally, part of these children remained in Sweden after the war. There is no clear collective memory, only individual memories; the collective memory of the war children has partly been shaped later through the activities of the war child associations. The main difference between the children evacuated in Finland (for example from Karelia to safer areas with their families) and the war children, who were sent abroad, is that the war children lack a shared story and experience with their families. They were outsiders . The whole matter is sensitive to many of such mothers and discussing the subject has often been avoided in families. The war-time censorship has continued in families through silence and avoidance and Finnish politicians and Finnish families had to face each other on this issue after the war. The lack of all-inclusive historical research has also prevented the formation of a collective awareness among war children returned to Finland or those remaining permanently abroad.. Knowledge of historical facts will help war-children by providing an opportunity to create an all-inclusive approach to the past. Personal experiences should be regarded as part of a large historical entity shadowed by war and where many political factors were at work in both Finland and Sweden. This means strengthening of the cognitive dimension discussed in Rüsen´s all-inclusive historical approach.

Physicochemical studies on the gelation of hen's egg yolk: Delipidation of yolk plasma by treatment with phospholipase-C and extraction with solvents

A method for the delipidation of egg yolk plasma using phospholipase-C, n-heptane, and 1-butanol has been described. An aggregating protein fraction and a soluble protein fraction were separated by the action of phospholipase-C. The aggregating protein fraction freed of most of the lipids by treatment with n-heptane and 1-butanol was shown to be the apolipoproteins of yolk plasma, whereas the soluble proteins were identified as the livetins. Carbohydrate and the N-terminal amino acid analysis of these protein fractions are reported. A comparison of these protein fractions with the corresponding fractions obtained by formic acid delipidation of yolk plasma has been made. The gelation of yolk plasma by the action of phospholipase-C has been interpreted as an aggregation of lipoproteins caused by ionic interactions. The role of lecithin in maintaining the structural integrity of lipoproteins has been discussed.

Oncolytic Adenoviruses with Radiation Therapy for Treatment of Prostate Cancer

Prostate cancer is the most common cancer in males. Although many patients with localized disease can be cured with surgery and radiotherapy, advanced disease and especially castration resistant metastatic disease remains incurable, with a median life expectancy of less than 18 months. Oncolytic adenoviruses (Ads) are a new promising treatment against cancer due to their innate capacity to kill cancer cells. Viral replication in tumor cells leads to oncolysis and production of a multiplicity of new virions that are capable of further destroying cancerous tissue. Oncolytic Ads can be modified for tumor targeted infection and replication and be armed with therapeutic transgenes to maximize the oncolytic effect. Worldwide, clinical trials with oncolytic Ads have demonstrated good safety while the antitumor efficacy remains to be improved. Importantly, the best responses have been reported when oncolytic adenoviruses have been combined with standard cancer treatments, such as chemotherapy and radiation. Further, a challenge in many virotherapy approaches has been the monitoring of virus replication in vivo. Reporter genes have been extensively used as transgenes to evaluate the biodistribution of the virus and activity of specific promoters. However, these techniques are often limited to preclinical evaluation and not amenable to human use. The aim of the thesis was to find and develop new oncolytic Ads with maximum efficacy against metastatic, castration resistant prostate cancer and study them in vitro and in vivo combined to different forms of radiation therapy. Using combination therapy, we were aiming for better antitumor efficacy with reduced side effects. Capsid modified Ads for enhanced transduction were studied. Serotype 3 targeted chimera, Ad5/3, was found to have enhanced infectivity for prostate cancer and was used for developing new viruses for the study. Correlation between Ad-encoded marker peptide secretion and simultaneous viral replication was evaluated and the effects of radiotherapy on viral replication were studied in detail. We found that the repair of double strand breaks caused by ionizing radiation was inhibited by adenoviral proteins and led to autophagic cell death. Both subcutaneous models and intrapulmonary tumor models mimicking metastatic, aggressive disease were used in vivo. Virus efficacy was evaluated by intratumoral injections. Also, intravenous administration was evaluated to study the effectiveness in metastatic disease. Oncolytic adenovirus treatment led to significant tumor growth control and increased the survival rate of the mice. These results were further improved when oncolytic Ads were combined with radiation therapy. Oncolytic Ads expressing human sodium/iodide transporter (hNIS) as a transgene were evaluated for their oncolytic potency and for the functionality of hNIS in vitro and in vivo. Monitoring of viral replication was also assessed using different imaging modalities relative to clinical use. SPECT imaging of tumor-bearing mice was evaluated and combined with simultaneous CT-scanning to obtain important anatomical information on biodistribution, also in a three-dimensional form. It was shown that hNIS-expressing adenoviruses could harbour a bi-functional transgene allowing for localization and imaging of viral replication. Targeted radiotherapy was applied by systemic radioiodide administration and resulted in iodide accumulation into Ad-infected tumor. The combination treatment showed significantly enhanced antitumor efficacy in mice bearing prostate cancer tumors. In summary, the results presented above aim to provide new treatment modalities for castration resistant prostate cancer. Molecular insights were provided for better understanding of the benefits of combined radiation therapy and oncolytic adenoviruses, which will hopefully facilitate the translation of the approach into clinical use for humans.