Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/β, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aβ lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aβ gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/β, are present in the proximal promoter of the mouse PP2A-Aβ gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/β all bind to PP2A-Aβ gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/β positively regulate the promoter of the PP2A-Aβ gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/β and the luciferase reporter gene driven by PP2A-Aβ promoter further confirm their control over the PP2A-Aβ promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/β can all bind to the PP2A-Aβ gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aβ gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aβ display distinct expression levels.
The histone acetyltransferase TIP60 regulates the DNA damage response following genotoxic stress by acetylating histone and remodeling chromatin. However, the molecular mechanisms underlying the TIP60-dependent response to UV-induced DNA damage remain poorly understood. To systematically analyse proteins that regulate TIP60 activity in response to UV irradiation, we performed a proteomic analysis of proteins selectively bound to TIP60 in response to UV irradiation using mass spectrometry and identified a novel regulatory mechanism by which TIP60 orchestrates transcriptional activation of p53-dependent checkpoint response in UV-irradiated cells. The initial step of this pathway involves UV-induced association of TIP60 with SUMO-conjugation enzymes and site-specific sumoylation of TIP60 at lysines 430 and 451 via Ubc9. This sumoylation initiates the relocation of TIP60 from nucleoplasm to the promyelocytic leukemia body, which is essential for the UV-irradiated DNA damage repair response via a p53-dependent pathway. Significantly, inhibition of TIP60 sumoylation by overexpression of non-sumoylatable mutant abrogates the p53-dependent DNA damage response, demonstrating the importance of TIP60 sumoylation in response to UV irradiation. Our biochemical characterization demonstrated that the sumoylation of TIP60 augments its acetyltransferase activity in vitro and in vivo. Thus, this study shed new light on the function and regulation of TIP60 activity in UV-irradiated DNA damage response.
The journey of rehabilitation for GC survivors is very long. The participants in this study faced different respective challenges during the diagnosis, treatment, and adjustment phases. Conventional disease-oriented medical care cannot satisfy the requirements of cancer patients because of patient-decentralized services. Our results indicate that GC survivors face diverse problems, both physically and mentally. Healthcare professionals should work to facilitate the psychological adjustment of cancer survivors and provide timely professional advice in combination with social resources. These results may serve as a reference for cancer care professionals who are navigating healthcare services.
The study purpose was to evaluate how much of the variance in quality of life (QOL) among Taiwanese patients with brain tumor could be accounted for by resilience and coping strategy. This cross-sectional study included 95 patients who had undergone a treatment of operations or chemotherapy or radiotherapy relevant to brain tumor after at least 1 month and completed the European Organization for Research and Treatment of Cancer QOL Questionnaire-Brain Cancer Module (EORTC QLQ-BN20), Resilience Scale (RS), and Ways of Coping Checklist-Revised (WCC-R). There was a significant negative correlation between resilience and future uncertainty QOL and motor dysfunction QOL. In addition, there was a significant positive correlation between the emotion-focused coping and future uncertainty QOL, as well as a significant negative correlation between problem-focused coping and motor dysfunction QOL. Resilience accounted for 4.8% and the emotion-focused coping accounted for 10.20% of the variance in separately predicting the future uncertainty QOL. This study highlights the potential importance of resilience and coping strategies in patients' QOL, which is relevant to brain tumor treatment.
Self-management programmes should be held regularly and evaluated in clinical practices, especially in developing countries. Providing practical screening tools and conducting psychological research on diabetes drive policy and health care system change.
Objective: The aim of the current study was to evaluate changes in treatment outcomes in terms of healthrelated quality of life (HRQoL) and symptom burden at zero, one, three, and six months after an initial diagnosis of colorectal cancer. The demographic and clinical characteristics that account for outcome changes in patients were investigated using a repeated measures framework. Methods and Materials: A cohort study was performed of 134 colorectal cancer patients followed from diagnosis to 6 months post-treatment in Central Taiwan. HRQoL and symptoms were assessed at diagnosis and one, three, and six months thereafter. The Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire, VAS pain, and the Memorial Symptom Assessment Scale (MSAS) were used for data collection. A generalized estimating equation (GEE) was applied for statistical analysis. Results: The majority of the patients were male (55%) and married (91.5%). The mean age was 60.4 years (SD = 11.71). Most were diagnosed stage III and IV colorectal cancer (54.5%). All underwent surgery; some also received chemotherapy (CT) or concurrent chemoradiation therapy (CCRT). The results of the GEE showed that overall, the HRQoL, pain, and symptoms of the patients significantly improved over the treatment period. Patients with stage IV disease who had received surgery and CCRT showed the worst HRQoL. Females, patients with comorbidity, and stage IV patients had higher pain scores over time. Female and stage IV patients had more severe physical symptoms, whereas stage II and IV patients had worse psychological symptoms over time. Conclusion: The patients' HRQoL, pain, and symptoms significantly improved over the 6-month treatment period. Certain patient and clinical variables accounted for changes in treatment outcomes regarding HRQoL and symptom burden in colorectal cancer patients.
Health professionals need to incorporate strategies to assist cancer patients' ability to engage in these behaviours and to manage situational impediments that may influence this ability. More importantly, clinicians need to assist patients to enhance their beliefs in their ability in overcoming various situation impediments for opioid-taking.
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