Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an oncofetal protein expressed in various cancers including leukemia. In this study, we assessed the role of IGF2BP1 in orchestrating leukemia stem cell properties. Tumor-initiating potential, sensitivity to chemotherapeutic agents and expression of cancer stem cell markers were assessed in a panel of myeloid, B-, and T-cell leukemia cell lines using gain-and loss-of-function systems, cross-linking immunoprecipitation (CLIP), and photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) techniques. Here we report that genetic or chemical inhibition of IGF2BP1 decreases leukemia cells' tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal HOXB4 and MYB and through regulation of expression of the aldehyde dehydrogenase, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
BackgroundAlkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China.MethodsWe enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1–Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3–6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes.ResultsOverall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19–3.96; P = 0.011] and patients in Q3 (76.8–92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14–0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0–76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes.ConclusionNon-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.
In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1α (HIF-1α) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density (MVD) was determined by CD31 staining. The results showed that the expression levels of NGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues (P<0.05). There was significant difference in the MVD between the NSCLC tissues (9.19±1.43) and para-cancerous lung tissues (2.23±1.19) (P<0.05). There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors (P<0.05). Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.
Background The prevalence of stroke recurrence, disability, and all-cause mortality of patients with minor ischemic stroke (MIS) remains problematic. The aim of the present study was to identify risk factors associated with adverse outcomes at 1 year after MIS in the Xi’an region of China. Methods This prospective cohort study included MIS patients above 18 years old with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 who were treated in any of four hospitals in Xi’an region of China between January and December 2015. The 1-year prevalence of stroke recurrence, disability, and all-cause mortality were evaluated, respectively. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. Results In this study, 131(10.5%, 131/1252) patients were lost to follow-up at 1 year. A total of 1121 patients were included for analysis, the prevalence of stroke recurrence, disability, and all-cause mortality at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause mortality. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. Conclusions The 1-year outcomes of MIS in Xi’an region of China were not optimistic, especially with a high prevalence of disability. The present study indicated that age and pneumonia were the common independent risk factors affecting the 1-year outcomes of MIS in Xi’an region of China.
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