Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

Background The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Methods Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Results Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Conclusions Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials

Perceptions and attitudes to sustainable roundworm control by European sheep farmers

Trabajo presentado al: 28th International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP). Dublín. 19-22 julio. Virtual meeting

Prediction of relapse-free survival according to adjuvant chemotherapy and regulator of chromosome condensation 2 (RCC2) expression in colorectal cancer

Background There is a need for improved selection of patients for adjuvant chemotherapy after resection of non-metastatic colorectal cancer (CRC). Regulator of chromosome condensation 2 (RCC2) is a potential prognostic biomarker. We report on the establishment of a robust protocol for RCC2 expression analysis and prognostic tumour biomarker evaluation in patients who did and did not receive adjuvant chemotherapy. Materials and methods RCC2 was analysed in 2916 primary CRCs from the QUASAR2 randomised trial and two single-hospital Norwegian series. A new protocol using fluorescent antibody staining and digital image analysis was optimised. Biomarker value for 5-year relapse-free survival was analysed in relation to tumour stage, adjuvant chemotherapy and the molecular markers microsatellite instability, KRAS/BRAF(V600E)/TP53 mutations and CDX2 expression. Results Low RCC2 expression was scored in 41% of 2696 evaluable samples. Among patients with stage I-III CRC who had not received adjuvant chemotherapy, low RCC2 expression was an independent marker of inferior 5-year relapse-free survival in multivariable Cox models including clinicopathological factors and molecular markers (HR 1.45, 95% CI 1.09 to 1.94, p=0.012, N=521). RCC2 was not prognostic in patients who had received adjuvant chemotherapy, neither in QUASAR2 nor the pooled Norwegian series. The interaction between RCC2 and adjuvant chemotherapy for prediction of patient outcome was significant in stage III, and strongest among patients with microsatellite stable tumours (p(interaction)=0.028). Conclusions Low expression of RCC2 is a biomarker for poor prognosis in patients with stage I-III CRC and seems to be a predictive biomarker for effect of adjuvant chemotherapy.Peer reviewe

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

The Children's Librarian As Viewed By Adults Served By Children's Services

Who are the adults using, wanting and interested in public library services to children? What proportion of users do they represent today in library children's rooms? Do librarians perceive the effects of present-day stresses, priorities, understanding and indifference of adults on public library services, both in terms of access and support? Are librarians aware that the field of public policy relating to children has reemerged?1 Answers to questions such as these need to be incorporated in an examination of children's services, present and potential, and of the "ideal" children's librarian. The adults using children's services in Connecticut public libraries are not unlike adults elsewhere. They are parents, teachers (particularly from early childhood education centers), college students, professional workers from community agencies and service organizations, artists (including commercial artists, writers and film-makers), grandparents, and adults seeking beginning-level information or recollecting childhood joys. Some adults are sophisticated library users while others are unfamiliar with the library environment.published or submitted for publicatio

Alternative og miljøvennlige behandlingsmetoder ved fiskesykdommer og parasittangrep i akvakultur. Rapport fra en studiereise til India og Filippinene 26 september - 10 oktober 1993

I perioden 26 september - 10 oktober 1994 gjennomførte forskningsleder Bjørn Braaten og forsker Halvor Hektoen en studiereise til Bhubaneswar, Orissa, India og Manila, Fillippinene. Hensikten med reisen var å skaffe tilveie informasjon om alternative og miljøvennlige behandlingsmetoder ved fiskesykdommer og parasittangrep og spesielt ved bruk av naturlige planter (herbal medicine). I tillegg ble flere forskningsinstitusjoner besøkt for opplysninger om forskningsprosjekter og sentrale problemstillinger i forbindelse med mulige framtidige bistandsprosjekter og bilateralt samarbeid. Følgende institusjoner ble besøkt: Central Institute of Freshwater Research (CIFA), Orissa University of Agriculture (OUAT), begge i Orissa, India, International Center for Living and Aquatic Resources Management (ICLARM), International Institute of Rural Reconstruction (IIRR) og Binangonan ferskvannsstasjon i Laguna de Bay, South East Asian Fisheries Development Center (SEAFDEC), alle tre i eller nær Manila, Filippinene

Resipientundersøkelser i Røyklibotn og forslag til gjennomføring av miljøtiltak ved Neptun Settefisk A/S

Resipientundersøkelsen har vist at Røyklibotn fra naturens side er en resipient med dårlig kapasitet. Dypbassenget i indre Røyklibotn har stagnant vann med lavt oksygeninnhold gjennom store deler av sommerhalvåret. På grunnlag av karbon- og nitrogeninnholdet i bunnsediment kunne imidlertid ikke resipienten betraktes som sterkt belastet. Belastningen fra Neptun Settefisk A/S må betraktes som liten i forhold til den naturlige belastningen. På grunn av resipientens lave kapasitet anbefales det likevel at fjordforbedringstiltak i form av neddykket ferskvannsutslipp settes i verk og eventuelt at rensing av avløpsvann fra settefiskanlegget gjennomføres.Neptun Settefisk A/