210 research outputs found
The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer
Although there is increasing appreciation of the role of the host inflammatory response in determining outcome in patients in colorectal cancer, there has been little concerted effort to favourably manipulate cancer-associated inflammation, either alone or in combination with current oncological treatment. Epidemiological and cardiovascular disease studies have identified aspirin, other nonsteroidal anti-inflammatory drugs and statins as potential chemotherapeutic agents which may manipulate the host inflammatory response to the benefit of the patient with cancer. Similarly, evidence of a chemotherapeutic effect of histamine-2 receptor antagonists, again mediated by an immunomodulatory effect, has previously led to increased interest in their use in gastrointestinal cancer. Extensive pre-clinical data and a limited number of clinical investigations have proposed a direct effect of these agents on tumour biology, with an anti-tumour effect on several of the hallmarks of cancer, including proliferative capacity, evasion from apoptosis and cell cycle regulation, and invasive capability of tumour cells. Furthermore, clinical evidence has suggested a pertinent role in down-regulating the systemic inflammatory response whilst favourably influencing the local inflammatory response within the tumour microenvironment. Despite such compelling results, the clinical applicability of nonsteroidal anti-inflammatory drugs, statins and histamine-2 receptor antagonists has not been fully realised, particularly in patients identified at high risk on the basis of inflammatory parameters. In the present review, we examine the potential role that these agents may play in improving survival and reducing recurrence in patients with potentially curative colorectal cancer, and in particular focus on their effects on the local and systemic inflammatory response
The relationship between aortic calcification and anastomotic leak following gastrointestinal resection: a systematic review
Anastomotic leak (AL) is a significant complication of gastrointestinal (GI) surgery. Impaired perfusion of the anastomosis is thought to play an important role. The degree of aortic calcification (AC) visible on preoperative CT imaging may be associated with an increased risk of AL following GI resection. This review assessed the relationship between AC and AL in patients undergoing GI resection. MEDLINE, EMBASE and the Cochrane library were systematically searched between 1946 and 2019. Relevant keywords were grouped to form a sensitive search strategy: surgical procedure (e.g. digestive system surgical procedure), calcification (e.g. vascular calcification, calcium score) and outcome (e.g. anastomotic leak). Studies assessing the degree of AC on preoperative imaging in relation to AL in adult patients requiring resection and anastomosis were included. The quality of each study was assessed using the Newcastle-Ottawa scale. Bias was assessed using the RevMan risk of bias tool. Nine observational studies were included: four in patients undergoing oesophageal resection (n=1446) and five in patients undergoing colorectal resection (n=556). AL occurred in 20% of patients following oesophagectomy and 14% of patients following colorectal resection. Adjustment for relevant confounders was limited in most studies. Two studies reported a relationship between the degree of AC and AL in patients undergoing oesophagectomy, independent of age and comorbidity. One study reported an association between AC and AL following colorectal resection, while three studies reported higher calcium scores in the iliac arteries of patients who developed colorectal AL. Overall study quality was moderate to good using the Newcastle-Ottawa scale. Detection and reporting bias was evident in the studies examining AL following colorectal resection. The current evidence suggests that the degree of AC may be associated with the development of AL, in particular in patients undergoing oesophagectomy. Further prospective data with adequate adjustment for confounders is required
Influence of Carbon Concentration on the Superconductivity in MgCxNi3
The influence of carbon concentration on the superconductivity (SC) in
MgCNi has been investigated by measuring the low temperature specific
heat combined with first principles electronic structure calculation. It is
found that the specific heat coefficient of the
superconducting sample () in normal state is twice that of the
non-superconducting one (). The comparison of measured
and the calculated electronic density of states (DOS) shows that the
effective mass renormalization changes remarkably as the carbon concentration
changes. The large mass renormalization for the superconducting sample and the
low (7K) indicate that more than one kind of boson mediated
electron-electron interactions exist in MgCNi.Comment: 4 pages, 4 figure
Role of dipolar and exchange interactions in the positions and widths of EPR transitions for the single-molecule magnets Fe8 and Mn12
We examine quantitatively the temperature dependence of the linewidths and
line shifts in electron paramagnetic resonance experiments on single crystals
of the single-molecule magnets Fe and Mn, at fixed frequency, with
an applied magnetic field along the easy axis. We include inter-molecular
spin-spin interactions (dipolar and exchange) and distributions in both the
uniaxial anisotropy parameter and the Land\'{e} -factor. The temperature
dependence of the linewidths and the line shifts are mainly caused by the
spin-spin interactions. For Fe and Mn, the temperature dependence of
the calculated line shifts and linewidths agrees well with the trends of the
experimental data. The linewidths for Fe reveal a stronger temperature
dependence than those for Mn, because for Mn a much wider
distribution in overshadows the temperature dependence of the spin-spin
interactions. For Fe, the line-shift analysis suggests two competing
interactions: a weak ferromagnetic exchange coupling between neighboring
molecules and a longer-ranged dipolar interaction. This result could have
implications for ordering in Fe at low temperatures.Comment: published versio
Coulomb gap in a model with finite charge transfer energy
The Coulomb gap in a donor-acceptor model with finite charge transfer energy
describing the electronic system on the dielectric side of the
metal-insulator transition is investigated by means of computer simulations on
two- and three-dimensional finite samples with a random distribution of equal
amounts of donor and acceptor sites. Rigorous relations reflecting the symmetry
of the model presented with respect to the exchange of donors and acceptors are
derived. In the immediate neighborhood of the Fermi energy the the
density of one-electron excitations is determined solely by
finite size effects and further away from is described by
an asymmetric power law with a non-universal exponent, depending on the
parameter .Comment: 10 pages, 6 figures, submitted to Phys. Rev.
The Glasgow Microenvironment Score and risk and site of recurrence in TNM I–III colorectal cancer
Background:
Glasgow Microenvironment Score (GMS) stratifies long-term survival into three groups based on tumour phenotype: peritumoural inflammation (Klintrup–Mäkinen (KM)) and tumour stroma percentage (TSP). However, it is not known if the location of disease recurrence is influenced by the GMS category.
Methods:
Seven hundred and eighty-three TNM I–III colorectal cancers (CRC) were included. GMS (GMS0—high KM; GMS1—low KM, low TSP; GMS2—low KM, high TSP) and cancer-specific survival (CSS), overall survival (OS) and disease recurrence were assessed using Cox regression analysis.
Results:
Of the 783 patients, 221 developed CRC recurrence; 65 developed local recurrence + systemic disease. GMS was independent for CSS (HR 1.50, 95% CI 1.17–1.92, p < 0.001) and OS (HR 1.23, 1.05–1.44, p = 0.01). Higher GMS category was associated with T-stage, N-stage, emergency presentation and venous invasion. GMS was independent for local+systemic recurrence (HR 11.53, 95% CI 1.45–91.85, p = 0.04) and distant-only recurrence (HR 3.01, 95% CI 1.59–5.71, p = 0.002). GMS 2 disease did not appear to have statistically better outcomes with adjuvant chemotherapy in high-risk disease.
Conclusion:
Although confounded by a higher rate of T4 and node-positive disease, GMS 1 and 2 are associated with an increased risk of local and distant recurrence. GMS is an independent poor prognostic indicator for recurrent colorectal cancer. Higher GMS patients may benefit from enhanced postoperative surveillance
A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with stage II/III colorectal cancer
It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial–mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15–3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17–6.86, p < 0.001) were associated with decreased cancer‐specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T‐cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer‐specific survival independent of TNM‐stage (HR 4.12 95% CI 2.30–7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade
The PHENIX Experiment at RHIC
The physics emphases of the PHENIX collaboration and the design and current
status of the PHENIX detector are discussed. The plan of the collaboration for
making the most effective use of the available luminosity in the first years of
RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program
available at http://www.rhic.bnl.gov/phenix
The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer
Background:
The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy.
Methods:
Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction.
Results:
GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012).
Conclusions:
This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX
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