Cytokinin response factor 6 represses cytokinin-associated genes during oxidative stress

Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy

Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy

Measuring changes in self-concept: a qualitative evaluation of outcome questionnaires in people having acupuncture for their chronic health problems

BACKGROUND: Changes in self-concept are an important potential outcome for many interventions for people with long-term conditions. This study sought to identify and evaluate outcome questionnaires suitable for quantifying changes in self-concept in people with long-term conditions, in the context of treatment with acupuncture and Chinese medicine. METHODS: A literature search was followed by an evaluation of three questionnaires: The Wellbeing Questionnaire W-BQ12, the Patient Enablement Instrument (PEI), and the Arizona Integrative Outcome Scale (AIOS). A convenience sample of 23 people completed the questionnaires on two occasions and were interviewed about their experience and their questionnaire responses. All acupuncturists were interviewed. RESULTS: Changes in self-concept were common and emerged over time. The three questionnaires had different strengths and weaknesses in relation to measuring changes in self-concept. The generic AIOS had face validity and was sensitive to changes in self-concept over time, but it lacked specificity. The PEI was sensitive and specific in measuring these changes but had lower acceptability. The sensitivity of the W-BQ12 was affected by initial high scores (ceiling effect) and a shorter timescale but was acceptable and is suitable for repeated administration. The PEI and W-BQ12 questionnaires worked well in combination. CONCLUSION: Changes in self-concept are important outcomes of complex interventions for people with long-term illness and their measurement requires carefully evaluated tools and long-term follow-up. The literature review and the analysis of the strengths and weaknesses of the questionnaires is a resource for other researchers. The W-BQ12 and the PEI both proved useful for this population and a larger quantitative study is planned

Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK)

BACKGROUND: Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity. PATIENTS AND METHODS: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC). RESULTS: The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories. CONCLUSION: Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated