Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. ...One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.
The ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells' niche as well as impart distant effects on remote cells with a similar molecular profile.
It is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.
The purpose of this study is to evaluate the use of density measurements in the diagnosis of an underlying residual tumor beyond iodine depositions after Lipiodol-based conventional transarterial ...chemoembolization (cTACE).
Thirty follow-up CT scans of 20 patients 6-12 weeks after Lipiodol-based cTACE, receiving a digital subtraction angiography at the same time, were analyzed. Reference for the detection of a residual tumor was the angiography, and a visible contrast enhancement was categorized as a residual tumor (n = 16 with residual tumor; n = 14 without residual tumor). The density of the iodine depositions was measured in all containing slices in non-contrast-, arterial- and portal venous-phase CT scans, with a slice thickness of 5.00 mm. The mean density of the iodine deposition during the portal venous phase was subtracted from the mean density of the arterial phase to calculate the density changes (a positive enhancement score represents washout in the portal venous phase). In addition, a quotient relating to the non-contrast measurement was evaluated.
Patients with a residual tumor displayed significantly higher enhancement scores in favor of density reduction between the arterial and portal venous phases, compared to patients without a residual tumor (1.41 ± 3.59, n = 14 vs. -13.97 ± 2.88, n = 16; p-value < 0.01). Furthermore, 87.75% of patients with an enhancement score higher than -1.00 (n = 9) had a residual tumor, whereas 100.00% of patients with an enhancement score lower than -20.00 (n = 6) were shown to be tumor-free. The enhancement score quotient resulted in similar findings.
After cTACE in patients with hepatocellular carcinoma (HCC), the presence of a viable tumor correlated with enhancement scores based on the density measurements of iodine depositions in different phases of the CT scan. Low enhancement scores were associated with completely treated tumors and can aid the decision process to avoid possibly unnecessary angiographies.
Purpose To compare adverse events and survival outcomes, including cancer-specific survival and overall survival (OS), in patients with T1aN0M0 renal cell carcinoma (RCC) who are undergoing partial ...nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), or active surveillance (AS). Materials and Methods Through use of the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 to 2011 with at least 1 year of consecutive follow-up, a HIPAA-compliant retrospective propensity score-matched study of patients with T1aN0M0 RCC who underwent PN, RN, TA, or AS was performed. Medicare beneficiaries (n = 10 218) with T1aN0M0 RCC as first primary cancer diagnosis were included. Survival and adverse health outcomes were compared across treatment groups. Results Overall, cancer-specific survival significantly differed in the PN versus RN (P < .001), AS versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4% versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively. With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-specific survival and OS for all AS comparisons were significantly lower. In addition, compared with the patients undergoing TA, those in the PN and RN groups had increased rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the procedure (P < .05 for all comparisons). Conclusion For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with surgical management, with significantly fewer adverse outcomes at 1 year after the procedure and similar rates of secondary cancer events compared with surgery.
The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In ...particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.
Impaired glucose tolerance is observed in depressed patients, and patients suffering from depression have an increased risk to develop diabetes mellitus. In depressed and diabetic patients, studies ...have shown both a beneficial effect of antidepressants on glucose homeostasis and the opposite. This review aims to structure the conflicting data and focuses on the question, which effect specific antidepressants have on glucose homeostasis. We therefore performed a systematic review of all available studies referenced in Medline from 1960 to 2011. We included antidepressant agents indexed in the Anatomical Therapeutic Chemical (ATC) classification system of the WHO in 2011 and searched for studies investigating their effects on glucose metabolism in clinical samples as well as in healthy subjects. Of 876 studies screened we included 66. Most studies had small sample sizes and lacked a placebo group limiting conclusions about antidepressant effects on glucose tolerance. However, some evidence points to beneficial effects on glucose homeostasis of hydrazine-type monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). In case of SSRIs, the effect is more pronounced in diabetic patients or patients with comorbid depression and diabetes mellitus. Noradrenegic substances (and possibly also dualacting antidepressants), in contrast, may deteriorate glucose tolerance. They can be used in depressed patients when favorable effects on mood outweigh adverse metabolic effects, but in depressed diabetics this can be at the expense of worsening of glycemic control. The effects of other antidepressants, like bupropione, mirtazapine or newer agents, require further investigation before reliable conclusions can be made. The synthesis of the findings is discussed in light of the specific pharmacodynamic properties of the antidepressants as well as the pathophysiological changes in depression and impaired glucose homeostasis, including animal studies.
The impact of solution pH has been investigated for the electrooxidation of formic acid on Au(111), taking the mole fraction of formate in solution as the relevant parameter. The electrocatalytic ...current density is increasing with rising pH and reaches a plateau for pH > 4. The pH-dependence of characteristic potentials shows systematic trends for the onset of the reaction, the peak maximum, and the phase transition within the formate adlayer. After the addition of phosphate buffer, a substantial deactivation by specific adsorption of phosphates and a bell-shaped curve for the maximum current density as a function of pH is found. The general behavior of co-adsorbing anions is addressed at low pH using various oxyanions to get more insight into the role of adsorbed formate. While non-carboxylate anions are displaced by formate at high potentials, mixed phases are observed for formate and other carboxylates.
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Background
To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic ...cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status.
Methods
In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA).
Results
About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients (P < 0.01). In Child‐Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child‐Pugh class A (n = 94), low‐NLR had higher OS vs high‐NLR (25.4 vs 12.2 months, P < 0.01). In Child‐Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low‐ vs high‐NLR: 6.7 vs 2.9 months, P = 0.2). Child‐Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124).
Conclusions
The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.
The neutrophil‐to‐lymphocyte ratio (NLR) has the strongest impact as a prognostic marker in intrahepatic cholangiocarcinoma (ICC) versus the platelet‐to‐lymphocyte ratio and systemic immune‐inflammation index, and increased NLR is associated with decreased survival in ICC. The NLR has decreased prognostic utility in patients with advanced liver disease.
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Faceting and nanostructuring of polycrystalline gold electrodes by cathodic corrosion in concentrated potassium hydroxide electrolytes has been systematically studied at different ...electrode potentials. Current-potential curves for the restructured Au electrodes in 0.1 M H2SO4 show characteristics of Au(111) in the double-layer and oxidation region. Thus, the modified Au electrodes adopt properties typically known for well-defined single crystal surfaces. Besides the preferential surface faceting, the electrochemically active surface area (EASA) is enhanced as a function of potential, concentration and time. Scanning electron micrographs show the formation of triangular pits and nanostructures with a specific orientation confirming the formation of (111)-facets. In this way, the behavior of single crystals is accompanied with the properties of nanoparticles which are of utmost interest in electrocatalysis and surface-enhanced Raman spectroscopy (SERS). The electrocatalytic activity of the newly formed “Au(111)” surface from an Au wire has been tested towards the hydrogen evolution reaction (HER) and for the formic acid oxidation reaction (FAOR). The study of electrocatalytic reactions at these nanostructured electrodes allows to identify active centers, which are absent for extended single crystal surfaces. Adsorbed pyridine on the nanostructured Au electrodes directly shows SERS activity, while untreated polycrystalline Au is SERS-inactive. The use of cathodic corrosion of simple wires is a paradigm of SERS-applications in electrochemistry with clean Au electrodes that provide properties of Au(111) single crystals.
The electrocatalytic hydrogen evolution reaction (HER) is employed to monitor the kinetics of potential-induced surface reconstruction of Au(111) in contact with either 0.1 M H2SO4 or 0.1 M HClO4 in ...the temperature range between 17 and 25 °C. An apparent activation energy varying between 0.6 and 0.7 eV is found for the reconstruction process at 20 °C in the potential range between −0.1 and −0.7 V vs. saturated mercury-mercurous sulfate electrode (MSE). The rate constant of the first-order formation kinetics shows an exponential dependence on electrode potential and decreases with more negative potentials. The potential-dependence is associated with an increase in bond strength for Au surface atoms with increasing negative excess charge. Specific adsorption of anions hinders surface reconstruction at potentials close to the potential of zero charge, while the presence of carbon monoxide causes a significant enhancement of the rate for potential-induced Au(111) reconstruction.
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•The hydrogen evolution reaction (HER) is used as structure-sensitive probe.•Au(111) surface reconstruction rate decreases for more negative potentials.•First-order kinetics is observed for potential-induced surface reconstruction.•The activation energy ranges from 0.6 to 0.73 eV.•Adsorption of carbon monoxide enhances surface reconstruction rate.
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