Buskvilstrup2937

The paper shows how the stratified MCDM technique in combination with the best-worst method (labelled stratified BWM) can be employed to compute the ranking of the available technologies. This research is expected to stimulate future applications of the stratified BWM to facilitate long-term decision making.Liver cancer is a leading cause of cancer deaths worldwide. Hepatocellular carcinoma (~75-85%) and cholangiocarcinoma (~10-15%) account for the majority of primary liver malignancies. Patients with primary liver cancer are often diagnosed with unresectable diseases and do not respond well to current therapies. The liver is also a common site of metastasis. Liver metastasis is difficult to treat, and the prognosis is poor. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive activity. MDSCs are an important component of the tumor microenvironment and promote tumor progression through various mechanisms. MDSCs expand in both liver cancer patients and mouse liver cancer models. Importantly, MDSCs correlate with poor clinical outcomes for liver cancer patients. The tumor-promoting functions of MDSCs have also been shown in mouse liver cancer models. All these studies suggest that targeting MDSCs can potentially benefit liver cancer treatment. This review summarizes the current findings of MDSC regulation in liver cancer and related disease conditions.

Previous clinical investigations have demonstrated that patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation have moderate responses to programmed cell death-1 and it's ligand-1 (PD-1/PD-L1) inhibitors, while some patients who failed EGFR-tyrosine kinase inhibitor (TKI) therapy could benefit from immunotherapy. As a result, we have explored alterations in the tumor immune microenvironment (TIME) before and after EGFR-TKI treatment to detect the chances and proper timing of immunotherapy among patients.

We identified 16 paired tissue samples pre- and post-EGFR-TKI treatment. Sections 4 μm thick were utilized to evaluate CD8, PD-L1, PD-1, LAG-3, and TIM-3 expressions by multiplexed fluorescent immunohistochemical staining. Five to ten representative original multispectral images of each sample were employed in the analysis.

Patients with positive CD8 + T-cell infiltration accounted for 37.5 % at baseline. Positive expression of PD-L1, PD1, LAG-3, and which proposed novel insights for rational use of LAG-3 inhibitors in advanced NSCLC patients with EGFR mutation.

Delta-like 1 homolog (DLK1) is a non-canonical Notch ligand known to be expressed in several cancers but whose role in lung cancer is not yet fully understood. We sought to confirm DLK1 expression in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), and to examine DLK1's clinical significance. Furthermore, we examined the possible utility of DLK1 as a novel target in radioimmunotherapy (RIT).

We retrospectively assessed the correlation between clinical features and DLK1 expression by immunohistochemistry in resected specimens from 112 patients with SCLC and 101 patients with NSCLC. Moreover, we performed cell and animal experiments, and examined the possibility of RIT targeting DLK1 in SCLC using iodine-125 (

I) -labeled anti-DLK1 antibody, knowing that

I can be replaced with the alpha-particle-emitter astatine-211 (

At).

In SCLC and NSCLC, 20.5 % (23/112) and 16.8 % (17/101) of patients (respectively) had DLK1-positive tumors. In NSCLC, DLK1 expression was associated with recurrence-free survival (P < 0.01) but not with overall survival. In SCLC, there was no association between DLK1 expression and survival. In addition,

I-labeled anti-DLK1 antibody specifically targeted DLK1 on human SCLC tumor cell lines. Furthermore,

I-labeled anti-DLK1 antibody was incorporated into tumor tissue in a mouse model.

A proportion of SCLC and NSCLC exhibits DLK1 expression. As a clinical feature, DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could serve as a new therapeutic target, including RIT, as suggested by our pilot study using a radiolabeled anti-DLK1 antibody in SCLC.

A proportion of SCLC and NSCLC exhibits DLK1 expression. As a clinical feature, DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could serve as a new therapeutic target, including RIT, as suggested by our pilot study using a radiolabeled anti-DLK1 antibody in SCLC.Renin Angiotensin System plays significant role in the memory acquisition and consolidation apart from its hemodynamic function in the pathophysiology of Alzheimer's disease (AD). It has been reported that Ang (1-7) ameliorates the cognitive impairment in experimental animals. However, the effect of Ang (1-7)/Mas receptor signaling is yet to be explored in Aβ42-induced memory impairment. Aβ42 was intracerebroventricularly injected into the male rats on day-1 (D-1) of the experimental schedule of 14 days. All the drugs were administered from D-1 to D-14 in the study design. Aβ42 significantly increased the escape latency during Morris water maze (MWM) test on D-10 to13 in the animals. Further, Aβ42 significantly decreased the time spent and percentage of total distance travelled in the target quadrant of the rats on D-14 in the MWM test. Aβ42 also significantly decreased the spontaneous alteration behavior on D-14 during Y-maze test. Moreover, there was a significant increase in the level of Aβ42, decrease in the cholinergic function (in terms of decreased acetylcholine and activity of cholinesterase, and increased activity of acetylcholinesterase), mitochondrial function, integrity and bioenergetics, and apoptosis in all the rat brain regions. Further, Aβ42 significantly decreased the level of expression of heme oxygenase-1 in all the rat brain regions. Ang (1-7) attenuated Aβ42-induced changes in the behavioral, biochemical and molecular observations in all the selected rat brain regions. Pyrrolidinedithiocarbamateammonium However, A779, Mas receptor blocker, significantly abolished the beneficial effects of Ang (1-7) in Aβ42-induced cognitive deficit animals. These observations clearly indicate that the Ang (1-7)/Mas receptor activation could be a potential alternative option in the management of AD.