Ovarian cancer is the leading cause of cancer‑ associated mortality in the female reproductive system. Interleukin (IL)‑33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by ...many cell types including epithelial cells. The role of IL‑33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL‑33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL‑33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase‑3 activity kit were all used to evaluate the direct effects of IL‑33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription‑polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL‑33; however, the relative caspase‑3 activity in cancer cells was decreased in the presence of IL‑33. Molecular mechanism studies revealed that the pro‑proliferative effect of IL‑33 on cancer cells was associated with decreased levels of p27, and the anti‑apoptotic effect of IL‑33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor‑related apoptosis‑inducing ligand receptor 1 (TRAILR1). Therefore, IL‑33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti‑tumor effort in pancreatic cancer, the results of the present study indicated that IL‑33 exhibited a significant onco‑promoting effect on ovarian cancer. Accordingly, the inhibition of IL‑33 may be a promising therapeutic strategy for ovarian cancer.
Abstract Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain ...limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The utilization of robotics in general surgery has increased significantly including usage in the Veterans Affairs (VA) system. We implemented a robotic inguinal hernia repair (RIHR) program in our ...VA hospital and report on initial experience with safety and outcomes. The first 100 consecutive RIHR at a VA hospital were reviewed and compared against the results of contemporaneous open inguinal hernia repair (OIHR). Data were collected for operative characteristics, surgical complications and pain related outcomes. Overall, operative times for OIHR were less than RIHR (83.7 vs. 109.7 min,
p
< 0.0001); however, there was no difference in operative time for bilateral repairs (121.5 vs. 121.9 min,
p
= ns). Complication rates were similar between the groups. RIHR patients had less pain at POD 1 than OIHR patients (
p
= 0.05). RIHR were less likely to have multiple post-op visits for pain than OIHR patients (
p
= 0.003). RIHR can be implemented in the VA system with acceptable surgical outcomes. RIHR may be associated with less post-operative pain in the early post-operative period.
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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
This paper starts out with a discussion of the importance of user-centred design, outlining its history and current embodiment in national and international standards and considers its particular ...relevance in addressing the needs of ageing populations. The paper moves on to examine how the premise of user-centred design has been taken up in education and focuses on the specific example of user-centred approaches as part of the Design and Technology requirement of the English National Curriculum, taught in England’s schools since 1989. The initial stage of the Designing our Tomorrow project presented in this paper was an investigation of the extent to which user-centred design was integrated in current teaching practice. Analysing baseline data collected from teachers and pupils at two state secondary schools the project team found that many of the tasks teachers planned for pupils did not provide opportunities to identify users’ needs when solving design problems. Finally, the paper presents a discussion of the project’s implications for pupils’ learning and understanding of Design and Technology.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on ...numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Primary gastrointestinal stromal tumors (GISTs) are typically treated with open resection. There is growing interest in laparoscopic GIST resection; however, data is limited. We report our ...experience with GIST resections using both open and laparoscopic techniques.
Materials and Methods
Twenty-nine GIST patients underwent definitive intent resection at the University of Missouri from 1990 to 2010. Patients who underwent laparoscopic resection (
n
= 7) were matched on the basis of tumor size, age, tumor location, and National Comprehensive Cancer Network (NCCN) risk stratification with seven patients who underwent open resection. The two groups were compared with respect to age, gender, BMI, tumor size, tumor site, mitotic rate, surgical margins, NCCN risk stratification, estimated blood loss, hospital stay, surgical complications, disease recurrence, and overall survival.
Results
The cohorts did not differ with respect to age, gender, BMI, tumor location, tumor size, or positive margins (
p
> 0.05). Patients who underwent open resection had more NCCN high-risk patients, but the difference was not statistically significant (
p
= 0.08). There was significantly less estimated blood loss (median 15 vs. 150 mL,
p
< 0.05) and significantly shorter hospital stay (median 4 vs. 7 days,
p
< 0.05) for the laparoscopy group. There were no recurrences in the laparoscopy group, but there was one in the open group with a median follow-up of 55 and 63 months, respectively (
p
> 0.05). Five-year disease-free survival was 100 % for the laparoscopic group and 83 % for the open resection group.
Conclusions
Laparoscopic resection for appropriately selected GISTs is feasible and associated with significantly less blood loss and shorter hospitalizations compared to open resection. Further studies are needed to better define its role for GIST.
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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
Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ...'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the long-term clinical significance of molecular upstaging in histopathology-negative, paraffin-embedded (PE) sentinel lymph nodes (SLNs) from melanoma patients.
Histopathologic ...evaluation can miss clinically relevant melanoma micrometastases in SLNs. This longitudinal correlative study is the first 10-year prognostic evaluation of a multimarker quantitative real-time reverse transcriptase-polymerase chain reaction (qRT) assay for PE melanoma-draining SLNs.
The SLN sections (n = 214) were assessed by qRT assay for 4 established messenger RNA biomarkers: MART-1, MAGE-A3, GalNAc-T, and PAX3.
The qRT assay upstaged 48 of 161 histopathology-negative (hematoxylin-eosin and immunohistochemistry) SLN specimens. At a median follow-up of 11.3 years for the entire cohort, estimated rates of 10-year overall survival (OS) and melanoma-specific survival (MSS) were 82% and 94%, respectively, for histopathology-negative/qRT-negative patients; 56% and 61%, respectively, for histopathology-positive patients; and 52% and 60%, respectively, for histopathology-negative/qRT-positive patients (P < 0.001 for OS, P < 0.001 for MSS). In a multivariate analysis of known melanoma prognostic factors, qRT positivity was significant (P < 0.05) for disease-free survival (hazard ratio HR, 4.3; 95% confidence interval (CI), 2.3-7.8), distant disease-free survival (HR, 6.6; 95% CI, 2.9-14.6), MSS (HR, 6.2; 95% CI, 2.6-14.4), and OS (HR, 2.8; 95% CI, 1.6-4.9).
The multimarker qRT assay has prognostic significance for molecular upstaging of PE melanoma-draining SLNs. Molecular upstaging of histopathology-negative SLNs confers a prognosis similar to that associated with SLN micrometastasis, and the number of positive qRT biomarkers is correlated to disease outcome.
The efficacy of radiation therapy (RT) for melanoma is limited in part by its radioresistance. Here, we examined the radiosensitizing effect of hydrogen peroxide (H(2)O(2)) on a radioresistant ...melanoma cell line, HTB-65. We found that H(2)O(2) synergized with RT to inhibit melanoma cell proliferation and promote apoptosis. The antiproliferative effect of H(2)O(2)/RT correlated with increased expression of p15 and reduced expression of cyclin D, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4. The pro-apoptotic effect of H(2)O(2) /RT correlated with reduced expression of the B-cell CLL/lymphoma (BCL)2. These data highlight the potential of H(2)O(2) as a radiation sensitizer for melanoma treatment and show that this warrants further study.
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