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Aim of the study was to evaluate the influence of clinical characteristics to the prognosis of disease and effectiveness of postoperative radiotherapy and adjuvant chemotherapy using lomustine, cisplatinum and vincristin in the treatment of children with medulloblastoma. This study was performed 2000 – 2005 in the Kaunas University of Medicine Hospital, department of children diseases. The data of patients, treated with medulloblastoma in 1994 - 2003, were used in this study. During ten-years period in Lithuania the medulloblastoma was diagnosed for 32 children. Twenty-seven of them were included in this study. The diagnostic tests made for the patients of the study: preoperative computer tomography or/and magnetic resonance imaging of brain; postoperative control computer tomography of brain; magnetic resonance imaging of spinal cord; bone scintigraphy with radioactive technetium; chest X-ray and ultrasound examination of the abdominal organs The spread of the disease and size of the residual postoperative tumor separates patients of this study into two: standard and high risk groups. Patients depending to the standard risk group were treated with radiotherapy alone. Patients included in the high risk group were treated by 2 different treatment methods: patients diagnosed with medulloblastoma between 1994 and 1998 were treated with craniospinal radiotherapy alone, other patients treated between 1999 and 2003 received radiotherapy with adjuvant chemotherapy with lomustine... [to full text]

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Background: Palliative gemcitabine has been shown to prevent the deterioration of well-being and to prolong survival of patients with pancreatic cancer in phase III randomized controlled trials (RCTs). It is unknown whether the efficacy reported in RCTs has translated into effectiveness in routine clinical practice. Objectives: 1) To describe the characteristics of patients with pancreatic cancer treated with palliative gemcitabine at the regional cancer centres (RCCs) of Ontario, 2) To describe: clinical benefit at two months, defined as stable or improved well-being; time to treatment discontinuation; and overall survival, 3) To identify factors associated with clinical benefit, and 4) To compare the effectiveness of gemcitabine with its reported efficacy in RCTs. Methods: This was a retrospective analysis of prospectively collected data. The study included patients with pancreatic cancer treated with palliative gemcitabine at the RCCs of Ontario between 2008 and 2011. Information about well-being was patient self-reported as captured by the Edmonton Symptom Assessment System (ESAS) at the RCCs. The proportions of patients that achieved clinical benefit were reported. Time to treatment discontinuation and overall survival were calculated using Kaplan –Meier survival analysis. Logistic regression was used to identify factors associated with clinical benefit. iii Results: The study population included 423 patients. Only 168 (39.1%) patients completed a pre-treatment ESAS. Patients completing a pre-treatment ESAS were not different than those that did not. Patients treated at RCCs were not different than those in RCTs. The median age of the study population was 65 years, 50% were male, 57% had stage IV disease and 94% had adenocarcinoma morphology. Thirty-seven percent of patients achieved clinical benefit at two months. Median time to treatment discontinuation and overall survival was 2 and 5.7 months, respectively. Stage and pre-treatment wellbeing were associated with clinical benefit at two months. Similar proportions of patients at RCCs and RCTs experienced clinical benefit. Time to treatment discontinuation and survival were similar as well. Conclusions: Efficacy of gemcitabine in RCTs has translated into effectiveness for patients treated at the RCCs of Ontario. It is unknown if this is true for patients not treated at the RCCs. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-08-01 17:50:00.185

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Cette etude pilote de six mois examinait si l'autogestion (AG) intensive par un agent secreteur d'insuline avait pour consequence une glycemie amelioree en comparaison avec une gestion standard (GS) chez les individus atteints de diabete de type 2. Des patients ont ete randomises soit a l'AG avec du repaglinide (n=8), ou du glyburide (n=6) ou a la GS (n=5). Des analyses biochimiques, alimentaires, comportementales, et d'activite physique ont ete effectuees. Les deux groupes de l'AG ont recu un enseignement d'autogestion en fonction du taux de glucose sanguin et une evaluation nutritionnelle qualitative. Le groupe AG (n=11) a suivi la cedule 65% du temps et a fait des ajustements 29% du temps. Une relation inverse significative a ete trouvee entre le changement de l'Alc et le pourcentage de temps d'ajustements accomplis correctement (r=0.64, p=0.035). La difference de masse corporelle entre l'AG et la GS n'etait pas significative, tout comme la masse corporelle moyenne a six mois. Une recherche plus approfondie avec un echantillon de plus grande taille serait necessaire afin d'explorer les avantages potentiels de la gestion du diabete via l'autogestion de medicaments oraux.

Over-expression of either P-gp1 and/or MRP1 in tumor cell lines confers resistance to structurally diverse anti-cancer drugs. Although the role of these two proteins in clinical drug resistance remains to be confirmed, the use of Pgp1-specific inhibitors in combination with standard anti-cancer drugs have demonstrated significant improvement in clinical response. However, evidence exists that reversal of P-gp1 alone is not sufficient. Therefore, while no drugs are currently available that can efficiently reverse MRP1 drug efflux in tumor cells, there is an urgent need to develop MRP1-specific blockers. In an effort to gain a better understanding of MRP1-drug interactions and to identify sequences within MRP1 that interact directly with drugs, we developed two structurally diverse photosensitive drug analogues, a quinoline-based compound (IACI) and a xanthone-derivative (IAARh123). Both compounds photolabeled MRP1 and showed a direct and specific interaction with the protein at physiologically relevant sites. Initial mapping of photolabeled sequences in MRP1 (Chapters 2 and 3), identified multiple IACI- or IAARh123-photolabeled peptides (∼4--7 kDa) derived from both the N-terminal (MSD0+MSD1+NBD 1) and C-terminal (MSD2+NBD2) domains of MRP1. A subsequent study (Chapter 4), using MRP1 variants with hemagglutinin (HA) epitopes inserted at eight different locations, led to a higher resolution mapping of the previously identified IACI- or IAARh123-labeled peptides. Specifically, two photolabeled peptides (∼6--7 kDa), derived from variants with insertions at positions 574 and 1222, were immunoprecipitated with anti-HA monoclonal antibody. Based on the location of the HA epitopes in the latter variants together with molecular masses of the two peptides, the photolabeled amino acid residues were localized to MRP1 sequences encoding transmembranes 10 and 11 of MSD1 and transmembranes 16 and 17 of MSD 2. Interestingly, the same sequences were photolabeled with both

Folate derivatives are required for nucleotide/DNA synthesis and DNA methylation. Methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylenctetrahydrofolate to 5-methyltetrahydrofolate, the folate derivative required for homocysteine remethylation to methionine, the precursor of S-adenosylmethionine. Approximately 45%--50% of the general population is heterozygous for a common substitution (677C &rarr; T, A to V) in MTHFR. Due to loss of heterozygosity (LOH) in cancer cells, individuals who are heterozygous for MTHFR in their constitutional DNA may contain only one of the above alleles in their tumor DNA. / Loss of heterozygosity of MTHFR was observed in 40% of ovarian carcinoma tumor samples and in 16% of colon carcinoma samples suggesting that the chromosomal location to which the MTHFR gene maps (1p36.3) undergoes frequent LOH. Examination of cell viability of human fibroblasts and of human colon carcinoma cell lines in minimum essential media (MEM) lacking methionine found both cell types to be extremely sensitive to the methionine deficiency. Replacing methionine with homocysteine and vitamin B12 restored the growth of normal fibroblast lines to levels that approached those of replete MEM, but the transformed lines increased proliferation only slightly under these conditions. These results support earlier reports regarding the increased methionine dependence of transformed lines. Targeting specific MTHFR variants with the antisense oligonucleotide resulted in &sim;50% decreased survival of two carcinoma cell lines (V/V genotype), possibly due to MTHFR's involvement in methionine synthesis. Allele-specific targeting of MTHFR could therefore provide an effective approach for cancer therapy. Furthermore, cancer patients with the V/V genotype may require less aggressive anti-folate chemotherapy since V/V carcinoma lines were highly sensitive to drug treatment (IC50 < 25 nM) whereas the A/A lines were more variable in response.

Bakgrund: Illamående kan uppkomma av många olika orsaker. En av dessa är illamående som uppkommer som en biverkning till cytostatikabehandling. Illamående är en känd biverkning av cytostatikabehandling, varför patienter som ska påbörja och genomgår behandling mot cancer erhåller profylaktisk antiemetikabehandling. Illamående kan få konsekvenser som försämrad nutritionsstatus, elektrolytrubbningar och i vissa fall kan patienten vilja avbryta sin behandling på grund av att illamåendet blir för jobbigt. Trots antiemetika fortsätter illamående att vara ett stort problem vid cytostatikabehandling. Syfte: Att beskriva olika omvårdnadsåtgärder som kan användas som ett komplement till antiemetika vid behandling av illamående orsakat av cytostatika. Metod: En litteraturstudie med grund i analys av kvantitativ forskning genomfördes. Resultat: Sökningar resulterade i fem omvårdnadsåtgärder: progressiv muskelavslappning, tillskott av ingefära, proteintillskott och ingefärskapslar, intag av druvjuice och musikterapi och bildspråk. Alla omvårdnadsåtgärder visade på en effekt på illamåendet i positiv riktning. Dock var resultaten motsägande inom vissa interventioner. Slutsats: Progressiv muskelavslappning, ingefära, druvjuice och musik och bildspråk kan eventuellt, som ett komplement till antiemetika, reducera illamående orsakat av cytostatikabehandling ytterligare. Dock krävs ytterligare forskning inom alla omvårdnadsåtgärder, då befintlig forskning ger otillräckliga eller motsägande resultat. Klinisk betydelse: Då antiemetika inte ger en fullgod effekt mot illamående kan omvårdnadsåtgärder fungera som ett komplement för att minska illamåendet ytterligare. / Background: There are many things that can cause nausea. One of these is chemotherapy. One of the most feared side-effects of chemotherapy is nausea. Untreated, nausea may give rise to consequences such as malnutrition, electrolyte imbalance and in some cases the patient might want to terminate their treatment because the nausea is unbearable. Nausea is a known side-effect to chemotherapy, and patients receive prophylactic antiemetic drugs. Even though patients receive antiemetic drugs, nausea keeps on being a problem while undergoing chemotherapy. Aim: The aim of this study was to describe different nursing interventions which can be used as a complement to antiemetic drugs. Method: A literature review with a basis in quantitative analyses was conducted. Results: Searches resulted in five nursing interventions: progressive muscle relaxation, ginger, protein and ginger, grape juice and music therapy and visual imagery. All of the five nursing interventions pointed towards a positive effect on nausea. But for some interventions contradictory studies were found that wasn’t as positive of the studied intervention. Conclusion: Progressive muscle relaxation, ginger, protein and ginger, grape juice and music therapy and visual imagery, might, as a complement to antiemetic drugs, reduce chemotherapy induced nausea even further than just antiemetic drugs. But more research in this area is needed, while existing research is insufficient. Clinical significance: While antiemetic drugs aren’t sufficient in treating chemotherapy induced nausea, nursing interventions can serve as a complement to reduce nausea even further.