ABSTRACT
@#The objective of this study wasto determine the factorial validity of the Chinese version of the General Family Functioning subscale (GF-12) and to assess parents’ perceived family functioning of children with or without chronic respiratory disease in Malaysia. Thirty two parents of children with chronic respiratory disease and 30 parents of healthy children were recruited. The GF-12 was administered at baseline and 2 weeks later. Confirmatory factor analysis showed that our instrument was a 1-factor model assessing general family functioning. Cronbach’s α value was 0.950. Test-retest reliability coefficient ranged from 0.490-0.790. The overall mean (standard deviation) score was not significantly different between parent’s perceived family functioning of children with or without respiratory disease [1.83(0.63) versus 1.65(0.46), p=0.385]. The Chinese version of the GF-12 was found to be a valid and reliable instrument to assess family functioning in Malaysia. Parents in the present study showed healthy perceived family functioning (total score >2.00)
ABSTRACT
Acute myeloid leukemia (AML) is currently treated with aggressive chemotherapy that is not well tolerated in many elderly patients, hence the unmet medical need for effective therapies with less toxicity and better tolerability. Inhibitors of FMS-like tyrosine kinase 3 (FLT3), JAK2 and histone deacetylase inhibitors (HDACi) have been tested in clinical studies, but showed only moderate single-agent activity. High efficacy of the HDACi pracinostat treating AML and synergy with the JAK2/FLT3 inhibitor pacritinib is demonstrated. Both compounds inhibit JAK-signal transducer and activator of transcription (STAT) signaling in AML cells with JAK2(V617F) mutations, but also diminish FLT3 signaling, particularly in FLT3-ITD (internal tandem duplication) cell lines. In vitro, this combination led to decreased cell proliferation and increased apoptosis. The synergy translated in vivo in two different AML models, the SET-2 megakaryoblastic AML mouse model carrying a JAK2(V617F) mutation, and the MOLM-13 model of FLT3-ITD-driven AML. Pracinostat and pacritinib in combination showed synergy on tumor growth, reduction of metastases and synergistically decreased JAK2 or FLT signaling, depending on the cellular context. In addition, several plasma cytokines/growth factors/chemokines triggered by the tumor growth were normalized, providing a rationale for combination therapy with an HDACi and a JAK2/FLT3 inhibitor for the treatment of AML patients, particularly those with FLT3 or JAK2 mutations.
ABSTRACT
BACKGROUND: The uptake of 2-[18F]-2-deoxy-D-glucose ((18)F-FDG) is widely used as a marker of increased glucose metabolism to monitor progression of cancers with positron emission tomography (PET). Many tumors have been shown to overexpress facilitated glucose transporters, especially GLUT-1 and a glycolytic enzyme, hexokinase II. PURPOSE: To define whether a quantitative relationship exists between the expression levels of GLUT-1 and hexokinase II, and (18)F-FDG uptake in human cancer xenografts. MATERIAL AND METHODS: We determined the expression levels of both GLUT-1 and hexokinase II in normal cells and in five different human cancer cell lines (AGS, A431, A549, Colo 320 HSR, and HepG2) using Western blot analysis. In vitro assays of 18F-FDG uptake in cultures were performed, and subsequently representative cell lines were inoculated onto the flanks of severe combined immunodeficient (SCID) mice. To establish an orthotopic model of human hepatocellular carcinoma (HCC), cells were injected into the intraportal vein of SCID mice. (18)F-FDG uptake in vivo was assessed by subjecting mice to PET imaging. RESULTS: All cell lines were shown to express higher amounts of GLUT-1 and hexokinase II compared with fibroblast controls. Our results from in vitro (18)F-FDG uptake assays also correlated with the Western blot results. All xenografts gave highly positive results at microPET imaging, and a strong correlation (R(2)=0.88, P<0.001) was found between the maximum standardized uptake values (SUV(max)) and the expression of GLUT-1 proteins. CONCLUSION: Our data indicate that the expression levels of GLUT-1 and hexokinase II as well as in vitro assays of FDG uptake serve as good screening tests to evaluate the feasibility of cell lines to be further developed into xenograft cancer models for small-animal PET imaging.
