999 resultados para Accelerate partial breast irradiation
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The cubiu (Solanum sessiliflorum) fruit, originating in the Amazon basin, is commonly used in that region for food, medicine, and cosmetics. In an experimental culture of cubiu, in order to evaluate its adaptation to conditions in the Northern region of the state of Rio de Janeiro, it was observed plants with mosaic symptoms. A cubiu plant was collected and analyzed to identify the etiological agent. After mechanical passage through a local lesion host, a host range test was performed. The virus induced chlorotic local lesions in Chenopodium quinoa, necrotic local lesions in Gomphrena globosa, mosaic in S. sessiliflorum, leaf and stem necrosis in tomato (Lycopersicon esculentum) 'Rutgers', mosaic and leaf distortion in Datura stramonium and Physalis floridana, and necrotic local lesions followed by systemic necrosis and plant death in four Nicotiana species. Electron microscopic observations of ultra thin sections from infected cubiu leaves showed the presence of spheroidal, membrane-bound particles typical of tospovirus species. Analysis of the nucleocapsid protein from concentrated virus particles indicated the presence of a 28 kDa protein. RT-PCR was performed after total RNA extraction from infected IPA-6 tomato leaves. A fragment of approximately 0,8 kbp corresponding to the N gene was amplified, cloned and sequenced. The N protein from the cubiu isolate was 95% homologous to the Groundnut ringspot virus (GRSV) protein, and no more than 85% homologous to those from Zucchini lethal chlorosis virus (ZLCV) and Chrysanthemun stem necrosis virus (CSNV), Tomato spotted wilt virus (TSWV), and Tomato chlorotic spot virus (TCSV). This is the first report of the occurrence of GRSV (or any other plant virus) in cubiu.
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Stunting and stem necrosis were noticed in soybeans (Glycine max) grown in 2000/2001 in West Central Brazil the same condition was also observed in the following year in plantations as far as 2,000 km from the initial area. Based on transmission (mechanical, graft, insect vector), purification and serology, electron microscopy and molecular studies the causal agent was determined to be a whitefly-borne carlavirus which is possibly related to Cowpea mild mottle virus (CpMMV).
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Cell migration and adhesion to the extracellular matrix (ECM) are crucial in many biological and pathological processes such as morphogenesis, tissue repair, inflammatory responses, survival, and cancer. Cell-matrix adhesion is mediated by the integrin family of transmembrane receptors, which not only anchor cells to their surroundings, but also transmit bidirectional signalling at the cell surface and couple the ECM to the cytoskeleton. Another group of adhesion receptors are the syndecan proteoglycans, which engage the ECM and possess signalling activity in response to a variety of ligands. Cell migration is a complex process that requires spatial and temporal coordination of adhesion, cell contractility, intracellular traffic of integrins, and matrix turnover by matrix metalloproteinases (MMPs). Thus, integrins and syndecans, as well as MMPs, play essential roles in cancer cell migration and invasion. The understanding of the cooperation of syndecans and integrins was broadened in this thesis study. The results reveal that syndecan-1 functions in concert with 21 integrin in cell adhesion to collagen, whereas syndecan-4 is essential in 21 integrin-mediated matrix contraction. Finally, oncogenic K-Ras was shown to regulate 21 integrin, membrane-type 1 MMP, and syndecan-1 and -4 expression and their cooperation in cell invasion. Epithelial-mesenchymal transition (EMT) is fundamental during embryogenesis and organ development. Activation of EMT processes, including the upregulation of mesenchymal intermediate filament protein vimentin, has also been implicated in the acquisition of a malignant phenotype by epithelial cancer cells. Members of the protein kinase C (PKC) superfamily are involved in cell migration and various integrindependent cellular functions. One aim of this work was to shed light on the role of vimentin in the regulation of integrin traffic and cell motility. In addition, the mechanism by which vimentin participates in EMT was investigated. The results show that integrin recycling and motility are dependent on the PKC–mediated phosphorylation of vimentin. In addition, vimentin was found to be a positive regulator of EMT and regulate the expression of several migratory genes. Specifically, vimentin governs the expression of receptor tyrosine kinase Axl, which is implicated in tumour growth and metastasis. Taken together, the findings described in this thesis reveal novel aspects of the complex interplay between distinct cellular components: integrins, syndecans, and the vimentin cytoskeleton, which all contribute to the regulation of human cancer cell adhesion, migration, and invasion.
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Bakgrunden och inspirationen till föreliggande studie är tidigare forskning i tillämpningar på randidentifiering i metallindustrin. Effektiv randidentifiering möjliggör mindre säkerhetsmarginaler och längre serviceintervall för apparaturen i industriella högtemperaturprocesser, utan ökad risk för materielhaverier. I idealfallet vore en metod för randidentifiering baserad på uppföljning av någon indirekt variabel som kan mätas rutinmässigt eller till en ringa kostnad. En dylik variabel för smältugnar är temperaturen i olika positioner i väggen. Denna kan utnyttjas som insignal till en randidentifieringsmetod för att övervaka ugnens väggtjocklek. Vi ger en bakgrund och motivering till valet av den geometriskt endimensionella dynamiska modellen för randidentifiering, som diskuteras i arbetets senare del, framom en flerdimensionell geometrisk beskrivning. I de aktuella industriella tillämpningarna är dynamiken samt fördelarna med en enkel modellstruktur viktigare än exakt geometrisk beskrivning. Lösningsmetoder för den s.k. sidledes värmeledningsekvationen har många saker gemensamt med randidentifiering. Därför studerar vi egenskaper hos lösningarna till denna ekvation, inverkan av mätfel och något som brukar kallas förorening av mätbrus, regularisering och allmännare följder av icke-välställdheten hos sidledes värmeledningsekvationen. Vi studerar en uppsättning av tre olika metoder för randidentifiering, av vilka de två första är utvecklade från en strikt matematisk och den tredje från en mera tillämpad utgångspunkt. Metoderna har olika egenskaper med specifika fördelar och nackdelar. De rent matematiskt baserade metoderna karakteriseras av god noggrannhet och låg numerisk kostnad, dock till priset av låg flexibilitet i formuleringen av den modellbeskrivande partiella differentialekvationen. Den tredje, mera tillämpade, metoden kännetecknas av en sämre noggrannhet förorsakad av en högre grad av icke-välställdhet hos den mera flexibla modellen. För denna gjordes även en ansats till feluppskattning, som senare kunde observeras överensstämma med praktiska beräkningar med metoden. Studien kan anses vara en god startpunkt och matematisk bas för utveckling av industriella tillämpningar av randidentifiering, speciellt mot hantering av olinjära och diskontinuerliga materialegenskaper och plötsliga förändringar orsakade av “nedfallande” väggmaterial. Med de behandlade metoderna förefaller det möjligt att uppnå en robust, snabb och tillräckligt noggrann metod av begränsad komplexitet för randidentifiering.
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The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.
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Background: In Finland, breast cancer (BC) is the most common cancer among women, and prostate cancer (PC) that among men. At the metastatic stage both cancers remain essentially incurable. The goals of therapy include palliation of symptoms, improvement or maintenance of quality of life (QoL), delay of disease progression, and prolongation of survival. Balancing between efficacy and toxicity is the major challenge. With increasing costs of new treatments, appropriate use of resources is paramount. When new treatment regimes are introduced into clinical practice a comprehensive assessment of clinical benefit, adverse effects and cost is necessary. Both BC and PC show a predilection to metastasize to bone. Bone metastases cause significant morbidity impairing the patients´ QoL. Diagnosis of bone metastases relies mainly on radiological methods, which however lack optimal sensitivity and specificity. New tools are needed for detection and follow-up of bone metastases. Aims: Anthracyclines and taxanes are effective chemotherapeutic agents in the treatment of metastatic breast cancer (MBC) with different mechanisms of action. Therefore, evaluation of the combination of anthracyclines with taxanes was a justifiable approach in the treatment of MBC patients. We assessed the efficacy, toxicity, cost of treatment and QoL of BC patients treated with first-line chemotherapy for metastatic disease with the combination epirubicin and docetaxel. We also evaluated the diagnostic potential of tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptides of type I collagen (ICTP) in the diagnosis of bone metastases in BC and TRACP 5b in PC patients. Results: The combination of epirubicin and docetaxel was effective in this phase II study, but required individual dose adjustment to avoid neutropenic infections, and the use of growth factors to maintain a feasible dose level. The response rate was 54 % (95 % CI 37-71) and the median overall survival (OS) was 26 months. Of the patients, 87 % were treated for infections. The treatment of adverse events required additional use of health resources mainly due to neutropenic infections, thereby raising direct treatment costs by 20 %. Despite adverse events, the global QoL was not significantly compromised during the treatment. Clinically evident acute cardiac toxicity was not observed. The combination of serum TRACP 5b and ICTP was at least equally sensitive and specific in detection of of bone metastases as commonly used total alkaline phosphatise (tALP) in BC patients. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC patients. Conclusions: Treatment with epirubicin and docetaxel showed high efficacy in first-line chemotherapy of MBC. The relatively high incidence of neutropenic infections requiring hospitalization increased the treatment costs. Despite adverse events, the global QoL of the patients was not significantly compromised. The combination of TRACP 5b and ICTP showed similar activity as tALP in detecting bone metastases in MBC. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC.
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This study analyzed the feasibility and efficacy of surgical therapies in patients with sleep-disordered breathing ranging from partial upper airway obstruction during sleep to severe obstructive sleep apnea syndrome. The surgical procedures evaluated were tracheostomy, laser-assisted uvulopalatoplasty (LUPP) and uvulopalatopharyngoplasty (UPPP) with laser or ultrasound scalpel. Obstructive sleep apnea and partial upper airway obstruction during sleep were measured with the static charge-sensitive bed (SCSB) and pulse oximeter. The patients with severe obstructive sleep apnea syndrome were treated with tracheostomy. Palatal surgery was performed only if the upper airway narrowing occurred exclusively at the soft palate level in patients with partial upper airway obstruction during sleep. The ultrasound scalpel technique was compared to laser-assisted UPPP. The efficacy of LUPP to reduce partial upper airway obstruction during sleep was assessed and histology of uvulopalatal specimen was compared to body fat distributional parameters and sleep study findings. Tracheostomy was effective therapy in severe obstructive sleep apnea. Partial upper airway obstruction and arterial oxyhemoglobin desaturation index during sleep decreased significantly after LUPP. The minimal retropalatal airway dimension increased and soft palate collapsibility decreased at the level where the velopharyngeal obstruction had occurred before the surgery. Ultrasound scalpel did not offer any significant benefits over the laser-assisted technique, except fewer postoperative haemorrhage events. The loose connective tissue as a manifestation of edema was the only histological finding showing correlation with partial upper airway obstruction parameters of SCSB. Tracheostomy remains a life-saving therapy and also long-term option when adherence to CPAP fails in patients with obstructive sleep apnea syndrome. LUPP effectively reduces partial upper airway obstruction during sleep provided that obstruction at the other levels than the soft palate and uvula were preoperatively excluded. Technically the ultrasound scalpel or laser surgeries are equal. In patients with partial upper airway obstruction the loose connective tissue is more important than fat accumulation in the soft palate. This supports the hypothesis that edema is a primary trigger for aggravation of upper airway narrowing during sleep at the soft palate level and evolution towards partial or complete upper airway obstruction during sleep.
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Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.
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The intensity-duration-frequency occurrence ratio (IDF) is a tool commonly used for precipitation-runoff data transformation, which is established from observations of intense precipitations over a period sufficiently long as to allow the occurrence of extremes at the observation site. This study focused on verifying the existence or absence of new data, in terms of IDF ratio, by using partial duration records produced from data on maximum daily disaggregated rainfall for pre determined durations. The partial duration records considered a base value of 55 mm, totaling 279 values. After the rainfall series were established, their independence and seasonality were assessed. Using the Student's t-test statistics, it was established that no new data, as IDF ratio, emerged from the analysis of the partial duration series with the recommended base value of precipitation, as compared to the historical records.
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This study aimed to verify the influence of partial dehydration of "Niagara Rosada" grape clusters in physicochemical quality of the pre- fermentation must. In Brazil, during the winemaking process it is common to need to adjust the grape must when the physicochemical characteristics of the raw material are insufficient to produce wines in accordance with the Brazilian legislation for classification of beverages, which establishes the minimum alcohol content of 8.6 % for the beverage to be considered wine. Therefore, given that the reduction in the water content of grape berries allows the concentration of chemical compounds present in its composition, especially the concentration of total soluble solids, we proceeded with the treatments that were formed by the combination of two temperatures (T1-37.1ºC and T2-22.9 ºC) two air speeds (S1: 1.79 m s-1 and S2: 3.21 m s-1) and a control (T0) that has not gone through the dehydration treatment. Analysis of pH, Total Titratable Acidity (TTA) were performed in mEq L-1, Total Soluble Solids (TSS) in ºBrix, water content on a dry basis and Concentration of Phenolic Compounds (CPC) in mg of gallic acid per 100g of must. The average comparison test identified statistically significant modifications for the adaptation of must for winemaking purposes, having the treatment with 22.9 ºC and air speed of 1.79 m s-1 shown the largest increase in the concentration of total soluble solids, followed by the second best result for concentration of phenolic compounds.
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In development of human medicines, it is important to predict early and accurately enough the disease and patient population to be treated as well as the effective and safe dose range of the studied medicine. This is pursued by using preclinical research models, clinical pharmacology and early clinical studies with small sample sizes. When successful, this enables effective development of medicines and reduces unnecessary exposure of healthy subjects and patients to ineffectice or harmfull doses of experimental compounds. Toremifene is a selective estrogen receptor modulator (SERM) used for treatment of breast cancer. Its development was initiated in 1980s when selection of treatment indications and doses were based on research in cell and animal models and on noncomparative clinical studies including small number of patients. Since the early development phase, the treatment indication, the patient population and the dose range were confirmed in large comparative clinical studies in patients. Based on the currently available large and long term clinical study data the aim of this study was to investigate how the early phase studies were able to predict the treatment indication, patient population and the dose range of the SERM. As a conclusion and based on the estrogen receptor mediated mechanism of action early studies were able to predict the treatment indication, target patient population and a dose range to be studied in confirmatory clinical studies. However, comparative clinical studies are needed to optimize dose selection of the SERM in treatment of breast cancer.
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En option är ett finansiellt kontrakt som ger dess innehavare en rättighet (men medför ingen skyldighet) att sälja eller köpa någonting (till exempel en aktie) till eller från säljaren av optionen till ett visst pris vid en bestämd tidpunkt i framtiden. Den som säljer optionen binder sig till att gå med på denna framtida transaktion ifall optionsinnehavaren längre fram bestämmer sig för att inlösa optionen. Säljaren av optionen åtar sig alltså en risk av att den framtida transaktion som optionsinnehavaren kan tvinga honom att göra visar sig vara ofördelaktig för honom. Frågan om hur säljaren kan skydda sig mot denna risk leder till intressanta optimeringsproblem, där målet är att hitta en optimal skyddsstrategi under vissa givna villkor. Sådana optimeringsproblem har studerats mycket inom finansiell matematik. Avhandlingen "The knapsack problem approach in solving partial hedging problems of options" inför en ytterligare synpunkt till denna diskussion: I en relativt enkel (ändlig och komplett) marknadsmodell kan nämligen vissa partiella skyddsproblem beskrivas som så kallade kappsäcksproblem. De sistnämnda är välkända inom en gren av matematik som heter operationsanalys. I avhandlingen visas hur skyddsproblem som tidigare lösts på andra sätt kan alternativt lösas med hjälp av metoder som utvecklats för kappsäcksproblem. Förfarandet tillämpas även på helt nya skyddsproblem i samband med så kallade amerikanska optioner.
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OBJECTIVE: to evaluate the accuracy of frozen section histopathology from fragments of tissue obtained by percutaneous core needle biopsy of palpable tumors in the diagnosis of breast cancer. METHODS: a cohort study was performed on 57 patients with palpable tumors and suspected breast cancer undergoing percutaneous thick needle core biopsy. The fragments were analyzed by the same pathologist. RESULTS: frozen section diagnosed 16 benign cases (28.6%) and 40 malignant (71.4%), whereas paraffin showed that 15 were benign (26.8%) and 41 malignant (73.2%). Histopathological examinations were concordant in 55 cases and there was one false-negative (6.2%). Statistics rates were: negative predictive value of 93.8%, positive predictive value of 100%, no false-positive (0%), one false negative (6.2%), specificity of 100%, sensitivity of 97 6%; observed agreement = 98.2%; expected agreement = 59.9%, Kappa = 0.955 [ 95% CI = 0.925-0.974, p < 0.01 ]. CONCLUSIONS: frozen section histopathological findings showed excellent correlation with the findings by the technique in paraffin in the fragments of palpable breast tumors obtained by thick needle percutaneous core biopsy (98.2% accuracy). Therefore, in these patients, it was possible to anticipate the diagnosis, staging and the breast cancer treatment planning.
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Breast cancer is the most frequent solid tumor among women and the leading cause of cancer related death in women worldwide. The prognosis of breast cancer patients is tightly correlated with the degree of spread beyond the primary tumor. In this thesis, the aim was to identify novel regulators of tumor progression in breast cancer as well as to get insights into the molecular mechanisms of breast cancer progression and metastasis. First, the role of phospholipid remodeling genes and enzymes important for breast cancer progression was studied in breast cancer samples as well as in cultured breast cancer cells. Tumor samples displayed increased de novo synthesized fatty acids especially in aggressive breast cancer. Furthermore, RNAi mediated cell based assays implicated several target genes critical for breast cancer cell proliferation and survival. Second, the role of arachidonic acid pathway members 15-hydroxyprostaglandin dehydrogenase (HPGD) and phospholipase A2 group VII (PLA2G7) in tumorigenesis associated processes was explored in metastatic breast cancer cells. Both targets were found to contribute to epithelial-mesenchymal transition related processes. Third, a high-throughput RNAi lysate microarray screen was utilized to identify novel vimentin expression regulating genes. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was found to promote cellular features connected with metastatic disease, thus implicating MTHFD2 as a potential drug target to block breast cancer cell migration and invasion. Taken together, this study identified several putative targets for breast cancer therapy. In addition, these results provide novel information about the mechanisms and factors underlying breast cancer progression.
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This three-phase study was conducted to examine the effect of the Breast Cancer Patient’s Pathway program (BCPP) on breast cancer patients’ empowering process from the viewpoint of the difference between knowledge expectations and perceptions of received knowledge, knowledge level, quality of life, anxiety and treatment-related side effects during the breast cancer treatment process. The BCPP is an Internet-based patient education tool describing a flow chart of the patient pathway during the breast treatment process, from breast cancer diagnostic tests to the follow-up after treatments. The ultimate goal of this study was to evaluate the effect of the BCPP to the breast cancer patient’s empowerment by using the patient pathway as a patient education tool. In phase I, a systematic literature review was carried out to chart the solutions and outcomes of Internet-based educational programs for breast cancer patients. In phase II, a Delphi study was conducted to evaluate the usability of web pages and adequacy of their content. In phase III, the BCPP program was piloted with 10 patients and patients were randomised to an intervention group (n=50) and control group (n=48). According to the results of this study, the Internet is an effective patient education tool for increasing knowledge, and BCPP can be used as a patient education method supporting other education methods. However, breast cancer patients’ perceptions of received knowledge were not fulfilled; their knowledge expectations exceed the perceived amount of received knowledge. Although control group patients’ knowledge expectations were met better with the knowledge they received in hospital compared to the patients in the intervention group, no statistical differences were found between the groups in terms of quality of life, anxiety and treatment-related side effects. However, anxiety decreased faster in the intervention group when looking at internal differences between the groups at different measurement times. In the intervention group the relationship between the difference between knowledge expectations and perceptions of received knowledge correlated significantly with quality of life and anxiety. Their knowledge level was also significant higher than in the control group. These results support the theory that the empowering process requires patient’s awareness of knowledge expectations and perceptions of received knowledge. There is a need to develop patient education to meet patients’ perceptions of received knowledge, including oral and written education and BCPP, to fulfil patient’s knowledge expectations and facilitate the empowering process. Further research is needed on the process of cognitive empowerment with breast cancer patients. There is a need for new patient education methods to increase breast cancer patients’ awareness of knowing.