Psychometric Properties of the Functional Assessment of Cancer Therapy-Neutropenia in Asian Cancer Patients With Chemotherapy-Induced Neutropenia.

CONTEXT: The Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) is a neutropenia-specific questionnaire to assess patients' health-related quality of life. OBJECTIVES: This study aimed to examine the psychometric properties of FACT-N among cancer patients with chemotherapy-induced neutropenia (CIN). METHODS: This prospective, cross-sectional study included multiethnic Asian cancer patients. Patients completed the questionnaires within seven days after diagnosed with CIN. Eligible patients completed either the English or Chinese version of the EuroQol 5-Dimensions (EQ-5D) and the FACT-N once, according to their language preference. The reliability was evaluated by using Cronbach alpha (α). The known-group validity was assessed based on patient's Eastern Cooperative Oncology Group performance status, neutropenia grade, and experience of fever. The convergent validity was evaluated by contrasting the FACT-N subscales with the EQ-5D domains. Multiple linear regression models were performed to compare the FACT-N total scores between the two language versions. RESULTS: A total of 276 eligible patients (200 English speaking and 76 Chinese speaking) were included in this study. Internal consistencies within the FACT-N subscales were satisfactory (Cronbach α = 0.71-0.85), except for the flu-like symptoms subscale (Cronbach α = 0.67). For known-group validity, the FACT-N total score could differentiate patients according to their Eastern Cooperative Oncology Group performance status (P < 0.001), neutropenia grade (P = 0.028), and experience of fever (P < 0.001). The correlations between the FACT-N subscales and their hypothesized constructs in EQ-5D domains were weak to moderate (|r| = 0.15-0.44). The measurement equivalence between the English and Chinese versions was established for the FACT-N total scores. CONCLUSION: The FACT-N is a valid and reliable instrument to be used in clinical practice to evaluate the health-related quality of life among multiethnic Asian patients with CIN.

Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells.

We have previously demonstrated that the total saponins of Astragalus membranaceus (AST) possess potential anti-tumorigenic effects in human colon cancer cells and tumor xenografts. In the present study, the proapoptotic effects of AST were investigated in native and cytokine-induced HT-29 cells to further unveil its mechanism of action. Growth-inhibitory action of AST (60 microg/ml) was demonstrated in native HT-29 cells, which was exaggerated in tumor necrosis factor (TNF) (5 ng/ml)-induced cells. These were accompanied by caspase 3 activation, cleavage of poly(ADP-ribose) polymerase and a subsequent increase in apoptotic cell numbers. Furthermore, activation of procaspase 8 indicates that the extrinsic apoptotic pathway was involved, while cleavage of Bid into t-Bid implicates cross-talk with the intrinsic apoptotic pathway. Alternatively, AST caused S and G2/M phase arrest, while in cytokine-induced cells S phase arrest was predominant. Further adding to our recent suggestion on its correlation with phosphatidylinositol 3-kinase (PI3K)-Akt signaling, we have now revealed that AST caused overexpression of PTEN and down-regulation of mammalian target of rapamycin (mTOR) expression. Nevertheless, these events were preceded by a decrease in nuclear factor-kappaB (NF-kappaB)/DNA binding activity with continuous ERK 1/2 activation. Some of these effects became more intense in cytokine-induced cells. Our findings in this study suggest that AST induces the extrinsic apoptotic cascade and causes cell cycle arrest in HT-29 cells by modulation of both mTOR and ERK signaling pathways, of which inhibition of NF-kappaB is important in the latter mechanism. Most of the above processes are more pronounced in cytokine-induced cells.