Chronic widespread pain (CWP) is associated with poor health-related quality of life (HRQoL). It is unclear whether pain itself is the cause of poor HRQoL or other factors play a role. We ...hypothesised that new onset of CWP was associated with poor physical and mental HRQoL but that psychosocial risk markers for CWP onset would explain this relationship. A prospective population-based survey measured pain and psychosocial status at baseline. Subjects free of CWP at baseline were followed up 15 months later, when pain status, threatening life events and HRQoL (SF-12) were assessed. The risk associated with the new onset of CWP and reporting poor SF12-MCS and SF12-PCS was quantified using multinomial logistic regression (relative risk ratios (RRRs) with 95% confidence intervals (95% CI)), adjusted for age and gender. 3000 subjects (77%) free of CWP at baseline participated at follow-up. 2650 subjects (88%) provided full SF-12 and pain data and formed the cohort for this analysis. 9.4% of subjects (n=248) reported new CWP. New CWP was associated with an increased risk of having the poorest SF12-MCS (RRR=2.3; 95% CI 1.6–3.2) and SF12-PCS (RRR=8.0; 95% CI 5.4–11.8) scores. After adjusting for baseline psychosocial status, the relationship between CWP onset and SF12-MCS was attenuated (RRR=1.2; 95% CI 0.8–1.8), although the association with SF12-PCS remained (RRR=4.8% CI 3.1–7.47). New onset of CWP is associated with poor mental and physical HRQoL. However, the relationship with mental HRQoL is explained by psychosocial risk markers.
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GEOZS, IJS, IMTLJ, KILJ, OILJ, SBCE, SBJE, UL, UPUK
Abstract Background This study investigated differences in cognitive performance between middle-aged adults with and without a lifetime history of mood disorder features, adjusting for a range of ...potential confounders. Methods Cross-sectional analysis of baseline data from the UK Biobank cohort. Adults aged 40–69 ( n = 143,828) were assessed using measures of reasoning, reaction time and memory. Self-reported data on lifetime features of major depression and bipolar disorder were used to construct groups for comparison against controls. Regression models examined the association between mood disorder classification and cognitive performance, adjusting for sociodemographic, lifestyle and clinical confounders. Results Inverse associations between lifetime history of bipolar or severe recurrent depression features and cognitive performance were attenuated or reversed after adjusting for confounders, including psychotropic medication use and current depressive symptoms. Participants with a lifetime history of single episode or moderate recurrent depression features outperformed controls to a small (but statistically significant) degree, independent of adjustment for confounders. There was a significant interaction between use of psychotropic medication and lifetime mood disorder features, with reduced cognitive performance observed in participants taking psychotropic medication. Conclusions In this general population sample of adults in middle age, lifetime features of recurrent depression or bipolar disorder were only associated with cognitive impairment within unadjusted analyses. These findings underscore the importance of adjusting for potential confounders when investigating mood disorder-related cognitive function.
Background
Age-related outcomes have become increasingly common in evaluating patients with melanoma. For instance, as age increases, sentinel node (SN) nonidentification increases and SN positivity ...decreases. Furthermore, advanced age is a risk factor for in-transit disease. We hypothesized that increasing age is accompanied by alterations in lymphatic function, possibly explaining these findings.
Methods
Our center’s melanoma database was queried to identify patients who underwent successful sentinel node biopsy after lymphoscintigraphy. Records of those treated between 2000 and 2005 were reviewed for age, sex, drainage basin, intraoperative radioactivity, and SN pathology.
Results
The 858 patients had a mean age of 55 years; 59% were men. Mean radioactivity in the hottest SN was 5232 counts per second; 179 patients (21%) had SN metastases. SN count rates were significantly and inversely related to age (
P
< .001 by Pearson correlation, analysis of variance, and χ
2
test). Mean counts per second were 6105, 5883, and 2720 for axillary, inguinal, and cervical basins, respectively (
P
< .01), and count rates in these basins were consistently lower with increasing age (neck and axilla,
P
< .001; groin,
P
= .060; Pearson correlation). Multivariate analysis confirmed an independent inverse association between age and count rates (
P
< .001), overall and within each primary tumor site.
Conclusions
Lymphatic function, as assessed by radiocolloid transit to and uptake within the SN, declines with age. Altered lymphatic function in older patients may modify metastatic patterns; knowledge of this may help clarify findings of reduced nodal positivity and increased in-transit disease in this population.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Radiotherapy (XRT) is used to improve local control of melanoma and for palliation of metastatic disease. Clinical use of XRT for melanoma is often limited by extent of disease ...and the relative radioresistance of melanoma may limit the effectiveness of XRT. Our group and others have previously shown that resveratrol (RSV) enhances radiation sensitivity in radioresistant prostate cancer cell lines. Material and Methods In this study, the effects of XRT in combination with RSV on radioresistant melanoma lines, SK-Mel-5 and HTB-65, were evaluated by assessment of proliferation and apoptosis. Clonogenic assay, comparison of proliferating cell nuclear antigen staining, Quick Cell Proliferation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate. Results We found that the percentage of colonies, proliferating cell nuclear antigen + cells and the optical density value of melanoma cells were decreased after addition of RSV to XRT (XRT/RSV). TUNEL + cells and the relative caspase-3 activity in melanoma cells were increased after addition of RSV to XRT (XRT/RSV). We investigated the possible molecular mechanisms of decreased proliferation and increased apoptosis by using reverse transcriptase-polymerase chain reaction and immunohistochemical staining. The anti-proliferative effect of XRT/RSV correlated with decreased expression of pro-proliferative molecule cyclin B, cyclin D, cdk2 and cdk4. The pro-apoptotic effect of XRT/RSV correlated with decreased expression of the anti-apoptotic molecule FLIP, Bcl-2, and survivin. Conclusion These data suggest that RSV enhances radiation sensitivity of melanoma cells by inhibiting proliferation and promoting apoptosis. Resveratrol may have a potential role as a radiation sensitizer for melanoma treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect ...on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Research highlights ► SIRT1 can function as both a tumor promoter and tumor suppressor. ► We summarize the available data regarding the role of SIRT1 in tumorigenesis. ► SIRT1 may play a dual role in ...different tissue contexts. ► The role of SIRT1 in tumorigenesis is poorly understood and more research is necessary to elucidate its function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Melanoma metastasis status is highly associated with the overall survival of patients; yet, little is known about proteomic changes during melanoma tumor progression. To better understand the changes ...in protein expression involved in melanoma progression and metastasis, and to identify potential biomarkers, we conducted a global quantitative proteomic analysis on archival metastatic and primary melanomas.
A total of 16 metastatic and 8 primary cutaneous melanomas were assessed. Proteins were extracted from laser captured microdissected formalin fixed paraffin-embedded archival tissues by liquefying tissue cells. These preparations were analyzed by a LC/MS-based label-free protein quantification method. More than 1500 proteins were identified in the tissue lysates with a peptide ID confidence level of >75%. This approach identified 120 significant changes in protein levels. These proteins were identified from multiple peptides with high confidence identification and were expressed at significantly different levels in metastases as compared with primary melanomas (q-Value<0.05).
The differentially expressed proteins were classified by biological process or mapped into biological system networks, and several proteins were implicated by these analyses as cancer- or metastasis-related. These proteins represent potential biomarkers for tumor progression. The study successfully identified proteins that are differentially expressed in formalin fixed paraffin-embedded specimens of metastatic and primary melanoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Osteoarthritis and the Rule of Halves Sheikh, L; Nicholl, B.I; Green, D.J ...
Osteoarthritis and cartilage,
04/2014, Volume:
22, Issue:
4
Journal Article
Peer reviewed
Open access
Summary Background Symptomatic osteoarthritis poses a major challenge to primary health care but no studies have related accessing primary care (‘detection’), receiving recommended treatments ...(‘treatment’), and achieving adequate control (‘control’). Objective To provide estimates of detection, treatment, and control within a single population adapting the approach used to determine a Rule of Halves for other long-term conditions. Setting General population. Participants 400 adults aged 50+ years with prevalent symptomatic knee osteoarthritis. Design Prospective cohort with baseline questionnaire, clinical assessment, and plain radiographs, and questionnaire follow-up at 18 and 36 months and linkage to primary care medical records. Outcome measures ‘Detection’ was defined as at least one musculoskeletal knee-related GP consultation between baseline and 36 months. ‘Treatment’ was self-reported use of at least one recommended treatment or physiotherapy/hospital specialist referral for their knee problem at all three measurement points. Pain was ‘controlled’ if characteristic pain intensity <5 out of 10 on at least two occasions. Results In 221 cases (55.3%; 95%CI: 50.4, 60.1) there was evidence that the current problem had been detected in general practice. Of those detected, 164 (74.2% (68.4, 80.0)) were receiving one or more of the recommended treatments at all three measurement points. Of those detected and treated, 45 (27.4% (20.5, 34.3)) had symptoms under control on at least two occasions. Using narrower definitions resulted in substantially lower estimates. Conclusion Osteoarthritis care does not conform to a Rule of Halves. Symptom control is low among those accessing health care and receiving treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic widespread pain (CWP) is a prevalent disorder associated with a low pain threshold and increased levels of psychological distress. Evidence indicates that there is a genetic component to CWP ...syndromes and pain sensitivity. Here we have identified and reviewed the current literature on genetic association (GA) studies of CWP and pain sensitivity by searching MEDLINE and EMBASE between January 1990 and May 2007. Of the 18 candidate genes studied to date, no definitive susceptibility genes have been identified. This review highlights the key issues for consideration when interpreting the findings from existing studies and in designing future studies to ensure robust and comparable findings in this field. Well-designed GA studies are essential if the genetic component to CWP aetiology is to be fully determined.
: Perforin and granzyme B are expressed primarily by activated lymphocytes (cytotoxic T cells, natural killer cells, and natural killer T cells) and function together to induce apoptosis of target ...cells. Typically, these proteins are not expressed in tumor cells. In the present study, we established the constitutive expression of perforin and granzyme B by the PC‐3 and DU145 prostate cancer (PCA) cell lines with reverse transcription polymerase chain reaction, immunohistochemistry, Western blot, or a combination of techniques. The combination of radiation and resveratrol (XRT/RSV) additively/synergistically decreased survival of PCA because, at least in part, of increased apoptosis. We further demonstrated that treatment with RSV up‐regulated the expression of both perforin and granzyme B, whereas treatment with XRT up‐regulated the expression of granzyme B, but not that of perforin. Combined XRT/RSV treatment of PCA cells further increased the expression of both perforin and granzyme B compared with RSV or XRT alone. Thus, increased radiosensitivity of prostate cancer cells induced by RSV correlated with up‐regulation of perforin and granzyme B, demonstrating a possible mechanism for tumor apoptosis. These findings might be helpful in devising new strategies for treating PCA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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