997 resultados para C-KI-RAS
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Purpose: To qualitatively explore the communication between healthcare professionals and oncology patients based on the perception of patients undergoing chemotherapy.Method: Qualitative and exploratory design. Participants were 14 adult patients undergoing chemotherapy at different stages of the disease. A socio-demographic and clinical data form was utilized along with semi-structured interviews. The interviews were audio-recorded, transcribed and content analysis was performed. Two independent judges evaluated the interview content in regards to emerging categories and obtained a Kappa index of 0.834.Results: Three categories emerged from the data: 1) Technical communication without emotional support, in which the information provided is composed of strictly technical information regarding the diagnosis, treatment and/or prognosis; 2) Technical communication, in which the information provided is oriented towards the technical aspects of the patient’s physical condition, while also providing psychological support for the patients’ subjective needs; and 3) Insufficient technical communication, win which there are gaps in the information provided causing confusion and suffering to the patient.Conclusions: Communication with emotional support contributes to greater satisfaction of chemotherapy patients. Practical implications: the results provide elements for the training of healthcare professionals regarding the importance of the emotional support that can be offered to cancer patients during their treatment.
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Background: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.
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Objectives/Introdution: Ki-67 protein has been used as an indicator of proliferation activity in tumor cells. In gastric cancer the prognostic value has not been fully understood. This study was designed to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Material/Methods: Seventy-two patients with gastric cancer were evaluated. These patients underwent gastric resection, and the tumor tissue was stained immunohistochemically. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. Ki-67 PI was correlated with clinicopathological characteristics and patient survival. Results: A low Ki-67 PI (less than or equal to 50%) was associated with poorly differentiated histology - diffuse type (p=0.009) and signet ring cells (p=0.004) - and younger age (p=0.022). A worse prognosis in patients with low Ki-67 PI was also found (a mean survival of 41.8 vs 63 months for high Ki-67 PI group), but not statistically significant (p=0.623, log rank test). Discussion/Conclusion: We found an inversely correlation between Ki-67 PI and histological differentiation grade. Patients in group with low Ki-67 PI are younger, with poorly differentiated histology and have a lower mean survival. Like other studies already suggested, we may have two different tumors phenotypes - highly invasive with low proliferative capability, and less invasive potential with higher proliferative ability. However, in this sample, no significant prognostic value was achieved between both.
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Sur le site de Ras el Bassit, durant les campagnes de fouilles menées de 1971 à 1984, 133 timbres amphoriques furent trouvés principalement dans le Tell du Meidan. Ces timbres sont des artefacts précieux. En effet, ce mémoire démontre comment les timbres amphoriques contribuent à l’élaboration de l’histoire d’un site, vue ici par l’analyse de ces 133 timbres amphoriques. Tout d’abord, les termes de base sont présentés pour expliquer ce que sont une amphore et un timbre. Par la suite, l’historiographie des recherches faites sur les timbres montre que, depuis le recueillement des informations sur les sites de production, certaines séries de timbres furent datés à l’année près, contribuant ainsi à améliorer les datations des autres sites. C’est de cette manière que les anses timbrées contribuent le plus souvent à améliorer un site. Il existe aussi d’autres apports. Par exemple, en localisant la production d’une série de timbres, les échanges commerciaux peuvent être aperçus. À travers l’analyse de ces 133 timbres, le site de Ras el Bassit pourra être mieux daté pendant l’époque hellénistique. En effet, les couches stratigraphiques en contexte pourront alors avoir un élément datable d’une grande précision, si tel est le cas. De plus, en connaissant la provenance de ces timbres amphoriques, elle démontrera que les échanges (avec des amphores timbrées) commencèrent dès le IVe siècle, ce qui correspond à une reprise des importations grecques. Ces importations dureront pendant toute l’époque hellénistique.
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W artykule autorzy podejmują się dokonania analizy zagadnienia dotyczącego możliwości naruszenia umowy spółki lub statutu przez członków zarządu oraz wpływu takiego naruszenia na ważność podjętej czynności prawnej. Zagadnienie to wywołuje liczne problemy praktyczne, chociażby z uwagi na obowiązek każdorazowej weryfikacji przed zawarciem umowy listy czynności, na dokonanie których statut lub umowa spółki zastrzega sobie taki wymóg. Nie ma tu znaczenia dobra czy zła wiara kontrahenta, który ma świadomość o istnieniu takiego zapisu dla ważności danej czynności prawnej. Zgoła odmienna jest sytuacja członka zarządu, dla którego uzyskanie takiej zgody jest ważne, z uwagi na naruszenia umowy spółki albo statutu, a w konsekwencji jego odpowiedzialność odszkodowawczą do dochodzenia ewentualnego odszkodowania za szkodę wyrządzoną działaniem lub zaniechaniem. Pamiętać jednak należy, że do istnienia odpowiedzialności niezbędne jest wykazanie szkody. Jednakże biorąc pod uwagę uwarunkowania biznesowe niekiedy trudno uzyskać zgodę rady nadzorczej lub walnego zgromadzenia wspólników na taką zgodę. Powstaje wtedy pytanie, czy można ją uzyskać następczo. Autorzy w artykule dokonują analizy stawiając tezę, iż możliwe jest następcze wyrażenie zgody na dokonaną bez uprzedniej zgody czynność prawną. Dokonując wnioskowania a maiori ad minus można w ocenie autorów dopuścić potwierdzenie takiej czynności następczo i to nie tylko w wymaganym dwumiesięcznym terminie, ale nawet późniejszym, co może mieć wpływ na ich ewentualne wyłączenie odpowiedzialności z tytułu naruszenia postanowień umowy spółki (statutu). Całość rozważań ściśle oscyluje wokół praktycznych problemów pojawiających się funkcjonowaniu spółki.
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Reactive oxygen species are a normal consequence of life in an aerobic environment. However when they deviate from the narrow permissible range in cells, oxidative damage can occur. Dictyostelium discoideum is a model organism ideal for the study of cell signaling events such as those affected by oxidative stress. It was previously shown that Ras signaling in Dictyostelium is affected by genetic inactivation of the antioxidant enzyme Superoxide dismutase C (SodC) and in vitro data suggests that the NKCD motif of Ras is the redox target of superoxide.^ The main objective of this project was to determine the mechanism of superoxide mediated Ras regulation in vivo. To accomplish the main objective, we cloned, and in some cases, mutated different Ras proteins and later determined their activity in wild type and sodC- cells. RasC and RasD showed normal activation in sodC- cells, however RasG and RasS displayed high Ras activity. These last two Ras proteins contain the NKC118D motif inside the nucleotide binding region. A mutation of cysteine 118 to alanine in RasG rendered the protein less active in sodC- than the wild type RasG protein and a mutation alanine118 to cysteine in RasD conferred redox sensitivity to this small GTPase. Additionally, the propensity of RasG to be targeted by superoxide was evident when the environment of wild type cells was manipulated to induce the internal generation of superoxide through changes in the extracellular ion levels mainly magnesium. Lack of magnesium ions increased the intracellular level of superoxide and severely hampered directional cell migration. Chemotaxis of cells expressing RasG was negatively impacted by the absence of magnesium ions; however rasG- cells did not seem to be affected in their ability to perform chemotaxis. The last experiment implies that RasG is an important mediator of cell signaling during oxidative stress, responsible for preventing cells from continuing their developmental program. Our study suggests that the cysteine residue in the NKCD motif is essential for mediating the redox sensitivity of Ras proteins in Dictyostelium and that RasG is an essential mediator of the response to oxidative stress in this organism.^
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Chronic telogen effluvium (CTE), a poorly understood condition, can be confused with or may be a prodrome to female pattern hair loss (FPHL). The pathogenesis of both is related to follicle cycle shortening and possibly to blood supply changes. To analyze a number of histomorphometric and immunohistochemical findings through vascular endothelial growth factor (VEGF), Ki-67, and CD31 immunostaining in scalp biopsies of 20 patients with CTE, 17 patients with mild FPHL and 9 controls. Ki-67 index and VEGF optical density were analyzed at the follicular outer sheath using ImageJ software. CD31 microvessel density was assessed by a Chalkley grid. Significant follicle miniaturization and higher density of nonanagen follicles were found in FPHL, compared with patients with CTE and controls. Ki-67+ index correlated positively with FPHL histological features. The FPHL group showed the highest VEGF optical density, followed by the CTE and control groups. No differences were found in CD31 microvessel density between the three groups. Histomorphometric results establish CTE as a distinct disorder, separate from FPHL from its outset. Its pathogenic mechanisms are also distinct. These findings support the proposed mechanism of 'immediate telogen release' for CTE, leading to cycle synchronization. For FPHL, accelerated anagen follicular mitotic rates and, thus, higher Ki-67 and VEGF values, would leave less time for differentiation, resulting in hair miniaturization.
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Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.
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Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.
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The SLC8A1 gene, which encodes the Na(+)/Ca(2+) exchanger, plays a key role in calcium homeostasis. Our previous gene expression oligoarray data revealed SLC8A1 underexpression in penile carcinoma (PeCa). The aim of this study was to investigate whether the dysregulation of SLC8A1 expression is associated with apoptosis and cell proliferation in PeCa, via modulation of calcium concentration. The underlying mechanisms of SLC8A1 underexpression were also explored, focusing on copy number alteration and microRNA. Transcript levels of SLC8A1 gene and miR-223 were evaluated by quantitative PCR, comparing PeCa samples with normal glans tissues. SLC8A1 copy number was evaluated by microarray-based comparative genomic hybridization (array-CGH). Caspase-3 and Ki-67 immunostaining, as well as calcium distribution by Laser Ablation Imaging Inductively Coupled Plasma Mass Spectrometry [LA(i)-ICP-MS], were investigated in both normal and tumor samples. Confirming our previous data, SLC8A1 underexpression was detected in PeCa samples (P=0.001) and was not associated with gene copy number loss. In contrast, overexpression of miR-223 (P=0.002) was inversely correlated with SLC8A1 (P=0.015, r=-0.426), its putative repressor. In addition, SLC8A1 underexpression was associated with decreased calcium distribution, high Ki-67 and low caspase-3 immunoexpression in PeCa when compared with normal tissues. Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to reduced calcium levels in PeCa and, consequently, to suppression of apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium-signaling axis may represent a potential therapeutic approach in PeCa.
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Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.
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In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67-positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67-positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67-positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30-positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.
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The p23 protein is a chaperone widely involved in protein homeostasis, well known as an Hsp90 co-chaperone since it also controls the Hsp90 chaperone cycle. Human p23 includes a β-sheet domain, responsible for interacting with Hsp90; and a charged C-terminal region whose function is not clear, but seems to be natively unfolded. p23 can undergo caspase-dependent proteolytic cleavage to form p19 (p231-142), which is involved in apoptosis, while p23 has anti-apoptotic activity. To better elucidate the function of the human p23 C-terminal region, we studied comparatively the full-length human p23 and three C-terminal truncation mutants: p23₁₋₁₁₇; p23₁₋₁₃₁ and p23₁₋₁₄₂. Our data indicate that p23 and p19 have distinct characteristics, whereas the other two truncations behave similarly, with some differences to p23 and p19. We found that part of the C-terminal region can fold in an α-helix conformation and slightly contributes to p23 thermal-stability, suggesting that the C-terminal interacts with the β-sheet domain. As a whole, our results suggest that the C-terminal region of p23 is critical for its structure-function relationship. A mechanism where the human p23 C-terminal region behaves as an activation/inhibition module for different p23 activities is proposed.
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Vitamin C stability and concentration was evaluated in isotonic beverages and B group vitamins (B1, B2, B3, B5 and B6) in power beverages. The amount of vitamins was found to be above of that declared on the labels, even after the shelf life had been exceeded. A small decrease in the amount of B group vitamins was observed during the shelf life of the products. In the case of vitamin C this decrease was slightly higher. The present research shows the need of increased quality control and inspection.
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Edibles films are an alternative to synthetic materials used for packing food products. Barbados cherry is rich in vitamin C and carotenoids. The aim of this study was to characterize and develop films by casting from cassava starch, lyophilized Barbados cherry pulp and glycerol. The films were characterized with respect to thickness, water vapor permeability (WVP), water solubility, vitamin C, carotene and mechanical properties. The interaction of pulp and glycerol reduced film thickness. An increase in pulp concentration up to 60% increased WVP but beyond this concentration reduced both WVP and solubility leading to an increased level of vitamin C and β carotene in the films.