instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: The quantity of the silver-stained nucleolar proteins (AgNOR proteins) measured in situ in cytohistologic preparations is related to the rapidity of cell proliferation. The term "AgNOR proteins" comprises several proteins. The relationship between the individual AgNOR protein amount and cell proliferating activity is not yet known. We studied the quantitative distribution of the individual AgNOR proteins, with specific attention to the two major AgNOR proteins, nucleolin and protein B23, in seven human cancer cell lines characterized by different cell doubling times.', 'The doubling time of cancer cells was measured by counting the asynchronously growing cells at regular time intervals. The AgNOR proteins were quantified in situ, after a specific one-step staining procedure, by computerized image analysis. For the quantitative evaluation of nucleolin and protein B23, two methods were followed. Nuclear proteins after separation by SDS-PAGE were transferred onto nitrocellulose membranes and were either: 1) stained by the silver staining procedure for AgNOR proteins or 2) treated with anti-nucleolin and anti-protein B23 mAb followed by reaction with secondary Ab linked to peroxidase and revealed by chemiluminescence and autoradiography. In both cases, measurement of individual AgNOR protein and nucleolin and protein B23 amount was carried out using computerized densitometric analysis.', 'Integrated density values of the silver-stained bands at 105 kDa (nucleolin) and 38 to 39 kDa (protein B23) represented, in all cell lines, more than 60% of the total silver-stained band value. A relationship was found between the densitometric values of silver-stained nucleolin and protein B23 and rapidity of cell proliferation (r = 0.85 and r = 0.86, respectively, p < 0.05). The values of nucleolin and protein B23 obtained using the Western blots were strictly related to the rapidity of cell proliferation (r = 0.93 and 0.96, respectively, p < 0.001). Finally, a good correlation was observed between the mean AgNOR protein area value, as defined in cytologic preparations in situ, and nucleolin and protein B23 amounts as evaluated in silver-stained nitrocellulose membranes (r = 0.92 and r = 0.90, respectively, p < 0.01) and in Western blots (r = 0.95 and r = 0.94, respectively, p < 0.001).\Question: Is the quantity of nucleolar proteins nucleolin and protein B23 related to cell doubling time in human cancer cells?
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These data indicate that the quantitative changes of AgNOR proteins observed in cytohistologic preparations in situ mainly reflect the quantitative changes of nucleolin and protein B23 and demonstrate that nucleolin and protein B23 amounts are inversely related to cell doubling time in human cancer cells.

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Context: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets.', 'Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n=174).', 'Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p=0.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p=0.0019) as well as with cathepsin B and D (p0.0001) that are implicated in cell invasion and metastasis.\Question: Does uPAR enhance malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R?
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Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC.

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Context: The yield of screening programmes for Type 2 diabetes in the existing healthcare setting might be lower than anticipated from tests of screening algorithms in data from epidemiological surveys. Our aims were to evaluate the reliability of the algorithms and the effectiveness of a proposed stepwise screening programme for Type 2 diabetes in general practice.', 'The screening programme had four steps: (i) mail-distributed self-administered risk-chart; (ii) screening tests: random blood glucose (RBG) and HbA(1)c; (iii) diagnostic procedure 1 for fasting blood glucose (FBG) (if RBG >/=5.5 mmol/l or HbA(1)c >/=6.1%); and (iv) OGTT as diagnostic procedure 2 (if 5.6</=FBG<6.1 mmol/l or HbA(1)c >/=6.1%). Abnormalities of glucose metabolism were classified according to the WHO 1999 criteria, based on capillary whole blood. The subjects were all patients between 40 and 69 years of age ( n=60,926) who were registered in 88 general practices and had not been previously diagnosed with diabetes.', 'A total of 11,263 individuals had a high-risk risk-score and attended the screening consultation (step 1 test-positive). Of these, 30.1% needed diagnostic tests (step 2 test-positive) and 27.2% of these needed an OGTT (step 3 test-positive). The test-positive proportions were equal to the proportions obtained in data from a population-based survey from Step 2 onwards, and the algorithms were thus reliable. The identification rate was only 19% of all prevalent undiagnosed diabetes according to a recently published prevalence estimate. This was due to a large dropout rate among high-risk individuals prior to entry into the programme.\Question: Is population-based stepwise screening for unrecognised Type 2 diabetes ineffective in general practice despite reliable algorithms?
answer:
Population-based mail-distributed stepwise screening for Type 2 diabetes in general practice is ineffective, despite reliable screening algorithms, primarily because many high-risk individuals fail to participate.