75 research outputs found
A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer
Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer
Contextual factors in shared decision making: a randomised controlled trial in women with a strong suspicion of breast cancer
Decision aids in North American breast cancer outpatients have been shown to assist with treatment decision making and reduce decisional conflict. To date, appropriate delivery formats to effectively increase patient participation in newly diagnosed breast cancer inpatients have not been investigated in the context of German health care provision. The impact of a decision aid intervention was studied in patients (n=111) with a strong suspicion of breast cancer in a randomised controlled trial. The primary outcome variable was decisional conflict. Participants were followed up 1 week post-intervention with a retention rate of 92%. Analyses revealed that the intervention group felt better informed (ηp2=0.06) but did not experience an overall reduction in decisional conflict as compared with the control group. The intervention had no effect on uptake rates of treatment options, length of consultation with the surgeon, time point of treatment decision making, perceived involvement in decision making, neither decision related nor general patient satisfaction. Patients who received the decision aid intervention experienced a small benefit with regards to how informed they felt about advantages and disadvantages of relevant treatment options. Results are discussed in terms of contextual factors and individual differences as moderators of treatment decision aid effectiveness
Predicting general and cancer-related distress in women with newly diagnosed breast cancer
Background: Psychological distress can impact medical outcomes such as recovery from surgery and experience of side effects during treatment. Identifying the factors that explain variability in distress would guide future interventions aimed at decreasing distress. Two factors that have been implicated in distress are illness perceptions and coping, and are part of the Self-Regulatory Model of Illness Behaviour (SRM). The model suggests that coping mediates the relationship between illness perceptions and distress. Despite this; very little research has assessed this relationship with cancer-related distress, and none have examined women with screen-detected breast cancer. This study is the first to examine the relative contribution of illness perceptions and coping on general and cancer-related distress in women with screen-detected breast cancer.
Methods: Women recently diagnosed with breast cancer (N = 94) who had yet to receive treatment completed measures of illness perceptions (Revised Illness Perception Questionnaire), cancer-specific coping (Mental Adjustment to Cancer Scale), general anxiety and depression (Hospital Anxiety and Depression scale), and cancer-related distress.
Results: Hierarchical regression analyses revealed that medical variables, illness perceptions and coping predicted 50% of the variance in depression, 42% in general anxiety, and 40% in cancer-related distress. Believing in more emotional causes to breast cancer (beta = .22, p = .021), more illness identity (beta = .25, p = .004), greater anxious preoccupation (beta = .23, p = .030), and less fighting spirit (beta = -.31, p = .001) predicted greater depression. Greater illness coherence predicted less cancer-related distress (beta = -.20, p = .043). Greater anxious preoccupation also led to greater general anxiety (beta = .44, p < .001) and cancer-related distress (beta = .37, p = .001). Mediation analyses revealed that holding greater beliefs in a chronic timeline, more severe consequences, greater illness identity and less illness coherence increases cancer-specific distress (ps < .001) only if women were also more anxiously preoccupied with their diagnosis.
Conclusions: Screening women for anxious preoccupation may help identify women with screen-detected breast cancer at risk of experiencing high levels of cancer-related distress; whilst illness perceptions and coping could be targeted for use in future interventions to reduce distress
Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships
INTRODUCTION: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity, which is required for the ubiquitination of securin and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC activation is prevented. In addition, several APC-targeting molecules such as securin, polo-like kinase, aurora kinase, and SnoN have been reported to be oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis. However, the clinical significance and the involvement of APC in tumorigenesis have not been investigated. METHODS: The expression of APC7 was immunohistochemically investigated in 108 invasive ductal carcinomas of the breast and its relationship with clinicopathologic parameters was examined. The expression of APC7 was defined as positive when the summed scores of staining intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+. RESULTS: Positive APC7 expression was less frequent than its negative expression when histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P = 0.0016) was elevated. The frequency of APC7 negative expression was higher in high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups. CONCLUSION: These data show that loss of APC7 expression is more common in breast carcinoma cases with poor prognostic parameters or malignant characteristics. They therefore suggest that dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer
Nutrient Control of Yeast PKA Activity Involves Opposing Effects on Phosphorylation of the Bcy1 Regulatory Subunit
Kelch repeat proteins Gpb1 and Gpb2 control yeast PKA activity in response to nutrients by stimulating phosphorylation of the Bcy1 regulatory subunit. Gpb1 and Gpb2 function by blocking inhibition of Bcy1 phosphorylation by PKA catalytic subunits. Phosphorylated Bcy1 is more stable and is a more effective inhibitor of PKA activity
Contribution of Caspase(s) to the Cell Cycle Regulation at Mitotic Phase
Caspases have been suggested to contribute to not only apoptosis regulation but also non-apoptotic cellular phenomena. Recently, we have reported the involvement of caspase-7 to the cell cycle progression at mitotic phase by knockdown of caspase-7 using small interfering RNAs and short hairpin RNA. Here we showed that chemically synthesized broad-spectrum caspase inhibitors, which have been used to suppress apoptosis, prevented the cell proliferation in a dose-dependent manner, and that the subtype-specific peptide-based caspase inhibitor for caspase-3 and -7, but not for caspase-9, inhibited cell proliferation. It was also indicated that the BIR2 domain of X-linked inhibitor of apoptosis protein, functioning as an inhibitor for caspase-3 and -7, but not the BIR3 domain which plays as a caspase-9 inhibitor, induced cell cycle arrest. Furthermore, flow cytometry revealed that the cells treated with caspase inhibitors arrested at G2/M phase. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, the prevention of the cell proliferation by caspase inhibitors induced cell cycle arrest at mitotic phase accompanying the accumulation of the substrates for APC/C, suggesting the impairment of the APC/C activity at the transition from M to G1 phases. These results indicate that caspase(s) contribute to the cell cycle regulation at mitotic phase
APC/C-Mediated Degradation of dsRNA-Binding Protein 4 (DRB4) Involved in RNA Silencing
Background: Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized. Methodology/Principal Findings: In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA). This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2) of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed
B-Cyclin/CDKs Regulate Mitotic Spindle Assembly by Phosphorylating Kinesins-5 in Budding Yeast
Although it has been known for many years that B-cyclin/CDK complexes regulate the assembly of the mitotic spindle and entry into mitosis, the full complement of relevant CDK targets has not been identified. It has previously been shown in a variety of model systems that B-type cyclin/CDK complexes, kinesin-5 motors, and the SCFCdc4 ubiquitin ligase are required for the separation of spindle poles and assembly of a bipolar spindle. It has been suggested that, in budding yeast, B-type cyclin/CDK (Clb/Cdc28) complexes promote spindle pole separation by inhibiting the degradation of the kinesins-5 Kip1 and Cin8 by the anaphase-promoting complex (APCCdh1). We have determined, however, that the Kip1 and Cin8 proteins are present at wild-type levels in the absence of Clb/Cdc28 kinase activity. Here, we show that Kip1 and Cin8 are in vitro targets of Clb2/Cdc28 and that the mutation of conserved CDK phosphorylation sites on Kip1 inhibits spindle pole separation without affecting the protein's in vivo localization or abundance. Mass spectrometry analysis confirms that two CDK sites in the tail domain of Kip1 are phosphorylated in vivo. In addition, we have determined that Sic1, a Clb/Cdc28-specific inhibitor, is the SCFCdc4 target that inhibits spindle pole separation in cells lacking functional Cdc4. Based on these findings, we propose that Clb/Cdc28 drives spindle pole separation by direct phosphorylation of kinesin-5 motors
Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors
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