Search

• About 4–5% of CD4+ lymphocytes in TDLNs of BC had CD4+ CD25− FoxP3+CD127low/− phenotype. • A very small fraction of CD25− cells produce cytokines, lower than regulatory and effector subsets. • CD25− cells display an exhausted phenotype intermediate between effector and regulatory cells. • They have higher expression of IFNγ and IL-2 than Tregs but lower than effector subset. • Expression of IL-10 in this subset is significantly higher than effector but lower than Tregs. A T cell subtype with the CD4+ CD25− FoxP3+ phenotype was recently described. We aimed to investigate the frequency of these cells and their ability to produce cytokines in tumor-draining lymph nodes from patients with breast cancer (BC). Mononuclear cells from lymph nodes of 20 patients with BC were activated and stained for appropriate markers. The cells were assayed with four-color flow cytometry. A very small fraction of CD4+ CD25− FoxP3+ cells produced cytokines at levels that were significantly lower than in the regulatory (CD4+ CD25+ FoxP3+) and effector cell (CD4+ CD25+ FoxP3 −) subpopulations. The expression of IFNγ and IL-2 in the CD4+ CD25− FoxP3+ subset was significantly higher than in Treg cells, but lower than in the effector subset. Conversely, IL-22 expression in Treg cells was significantly higher than in the CD4+ CD25− FoxP3+ subpopulation. The expression of IL-10 in the CD4+ CD25− FoxP3+ subset was also significantly higher than in effector cells. We suggest that CD4+ CD25− FoxP3+ cells in patients with BC are exhausted cells with an intermediate phenotype between effector and regulatory cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Accumulation of Tfh, TFR and CD25− Treg cells in tumor draining lymph nodes (TDLNs). [•] In TDLNs, IL17 and IFNγ expression are decreased upon tumor progression. [•] In TDLNs, Treg and Th2 cells are increased in advance stages of disease. [Copyright &y& Elsevier]

• The ability of the nanoparticles to attach to SK-BR-3 cancer cells and collect them from the human whole blood as the cancer site. • Flow cytometry was used to examine the ability of antibody-conjugated nanoparticles to separate SK-BR-3 from the peripheral blood mononuclear cells environment in three different amounts of SK-BR-3 cells. • MNPs with Herceptin separated cancer cell in different quantity from human whole blood and PBMCs with much more efficiency compared with MNPs without antibody. Breast cancer is one of the leading causes of death among women worldwide, therefore early diagnosis and monitoring the status of cancer are essential. In the present study we developed antibody-conjugated iron oxide magnetic nanoparticles (MNPs) with highly efficient potential to detect HER2-expressing cancer cells in blood, a compartment where tumor cells are very rare. The MNPs were first coated with (3-aminopropyl) trimethoxysilane. Effective coating was checked by VSM, XRD, FT-IR, TGA, EDX, and SEM. Anti-HER2 antibody (Herceptin) was conjugated on the surface of silane-coated MNPs (MNP-Si). The affinity of antibody-conjugated MNPs (Ab/MNP-Si) for HER2-expressing cells was evaluated in the SK-BR-3 cell line as a breast cancer cell model. Different concentrations of SK-BR-3 cells were mixed with peripheral blood mononuclear cells and subjected to isolation with Ab/MNP-Si in a magnetic field. Separation efficiency, as determined by flow cytometry, was 77–98%. Further evaluation with fluorescence microscopy also confirmed the ability of Ab/MNP-Si to detect low numbers of SK-BR-3 cells in whole blood. Our results suggest that Ab/MNP-Si is a potentially useful tool to isolate circulating tumor cells by targeting tumor-specific surface receptors under a magnetic field, and may improve breast cancer diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

The relationship between salivary gland tumors and immune system has not been well inspected. We aimed to investigate the distribution of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells, CTLA4 + CD4 + lymphocytes, as well asIL-17 producing CD4 + and CD8 + (Th17 and Tc17) lymphocytes in peripheral blood of patients with benign and malignant salivary gland tumors and a group of healthy controls. Peripheral blood samples were obtained from 27 patients with salivary gland tumors (19 benign and 8 malignant; mean age of 49.2 ± 18.3), as well as19 age/sex matched healthy donors. Fluorochrome-conjugated antibodies were used to stain the cell surface markers, as well as intracellular molecules following cell-membrane fixation and permeabilization. The stained cells were acquired on a FACSCalibur four-color flowcytometer and analyzed by CellQuest Pro software package. The data were presented as mean percentages ± SEM. Results indicated that the patients with malignant salivary gland tumors have increased percentage of Treg cells (7.74 ± 1.1) and intracellular CTLA4 (inCTLA4)-positive CD4 + lymphocytes (8.18 ± 1.77) in comparison to the patients with benign tumors (4.38 ± 0.56 for Treg cells and 3.83 ± 0.56 for CTLA4 + CD4 + cells), as well as control subjects (2.34 ± 0.28 for Treg cells and 2.22 ± 0.25 for CTLA4 + CD4 + cells) ( p ≤ 0.001). Conversely these patients had reduced percentage of Th17 cells (0.84 ± 0.14) comparing to the patients with benign tumors (2.09 ± 0.31) as well as control subjects (2.31 ± 0.23) ( p ≤ 0.001). In addition, the ratio of Th17/Treg lymphocytes was significantly lower in both malignant (0.12 ± 0.03) and benign (0.48 ± 0.09) tumors in comparison to control subjects (1.26 ± 0.23) ( p < 0.001). The mean percentage of Tc17 cells in patients with benign (1.14 ± 0.15) and malignant (0.60 ± 0.13) tumors was nearly similar to those in control subjects (0.83 ± 0.14) but the mean expression intensityofIL-17 by these cells was significantly higher in patients with malignant tumors (11.06 ± 1.26) than controls (7.61 ± 0.69) ( p = 0.01). Increase in the prevalence of regulatory lymphocytes, Treg cells and CTLA4 + CD4 + lymphocytes, as well as the imbalance of Th17/Treg ratio may suggest the contribution of these immune effector cells in the progression of salivary gland tumors. From immune-regulatory point of view, these data also suggest that benign salivary gland tumors might fall between healthy and malignant conditions. The immunity to salivary gland tumors, as well as the findings presented here merits more in-depth investigation. [ABSTRACT FROM AUTHOR]

• PD-1 and PD-L expression on immune cells, especially in draining lymph nodes, is valuable for predicting prognosis and survival. • PD-1 and PD-L1 expression on tumor cells was not associated with BC prognosis. • The results highlight the significance of PD-L2 as a second important suppressive molecule in tumors. Bladder cancer (BC) can be successfully treated by manipulating immune responses with intravesical Bacillus Calmette-Guerin instillation or targeting the PD-1/PD-L signaling pathway. In the present study we investigated the prognostic significance of the immune checkpoint inhibitor PD-1 and its ligands PD-L1 and PD-L2 on tumor cells and infiltrating lymphocytes, in the tumor microenvironment and draining lymph nodes in patients with non-metastatic BC. Cells were mechanically isolated from tissues and draining lymph nodes from 58 patients, and surface-stained for CD45, PD-1, PD-L1 and PD-L2. The cells were then analyzed with a flow cytometric method. Approximately 2% of CD45-negative tumor and stromal cells expressed PD-L1. Expression was not associated with the main clinicopathological characteristics of the disease or with survival. However, as tumors progressed the frequency of PD-L1+CD45hi cells and the mean expression of PD-1 on CD45hi cells increased remarkably on immune cells in tumor tissues and draining lymph nodes. In addition, frequency analysis showed that cell percentages as well as mean expression of PD-L2 on total CD45+ lymphocytes and their CD45hi subpopulation in tumor-draining lymph nodes was significantly associated with cancer-related death (P < 0.05). Multiple Cox regression also revealed that while CD45+ (hazard ratio: 0.596, 95 % CI 0.439–0.809, P = 0.001) was associated with improved survival, CD45neg (HR: 0.615, 95 % CI 0.454–0.831, P = 0.002), and PD-L2+CD45+ cells (hazard ratio: 1.472, 95 % CI 1.023–2.120, P = 0.038) in draining lymph nodes were associated with lower survival. Our results suggest that in patients with BC, PD-1 and PD-L expression on immune cells, especially in draining lymph nodes, is valuable for predicting prognosis and survival, and possibly responsiveness to immunotherapy. However, expression of the inhibitor molecule or its ligands on tumor cells was not associated with prognosis. The results highlight the significance of PD-L2 as a second important suppressive molecule in tumors. [ABSTRACT FROM AUTHOR]

Herein we describe design and synthesis of new series of small quinazoline molecule connected to the azole moieties. Molecular docking screening were conducted on 102 various hybrids of quinazolinone and azole rings, toward epithelial growth factor receptor (EGFR). Among all screened compounds, six top-ranked hit hybrid scaffolds were finally selected ( 17a - 17f), synthesized and characterized by 1HNMR, 13CNMR and Mass spectroscopy. These molecules have been tested for their antiproliferative activities against two human cancerous cell lines (MCF-7 and A549) as well as normal cell line (MRC-5). Molecular dynamic (MD) simulation were also conducted on these series to show the key drug-target interactions. The results indicated that compound 1 7b , harboring imidazole moiety, showed strong inhibitory activity with IC 50 values of 1.38 ± 0.14 and 5.5 ± 0.09 μΜ against A549 and MCF-7 cell lines, respectively. MD simulation analysis revealed that H-bonds and hydrophobic interactions played an important role in the ligand binding stability. [Display omitted] [ABSTRACT FROM AUTHOR]

6-Methoxy-2-[(E)-Aryliminomethyl]-phenol (Aryl = Phenyl; 2,6-dimethyl; 2,6-diisopropylphenyl; 2,6-dichlorophenyl), comprising L 1 –L 4 ligands, and palladium complexes [Pd(L n ) 2 , n = 1–4] have been synthesized. The geometries of the [Pd(L n ) 2 ] complexes were derived from single X-ray crystallography experiments. The central Pd(II) ion is four-coordinated and surrounded by N 2 O 2 environment, adopting a square planar geometry. The ligand is bidentate, coordinating via imine nitrogen and phenolate oxygen atoms to the metal center. Analysis of the valence geometry within the phenolate rings suggests that in all complexes, the O1–C1 has a double bond character. FT-IR, 1 H, 13 C NMR and single X-ray crystal structures were reported. The cytotoxicity effect of four Pd(II) complexes was assessed on three cancerous cell lines: MCF-7 (breast carcinoma), A549 (lung carcinoma) and SKOV3 (ovarian carcinoma) and compared with that for cis -platin. One out of four metal complexes, Pd(L 1 ) 2 , exhibited the highest anti-proliferative activity on three investigated cancerous cells lines which is more effective than cis -platin. The results showed that this complex could effectively induce apoptotic death in cancerous cells, probably due to direct interaction by cellular DNA. [ABSTRACT FROM AUTHOR]

• Highly stable metal complexes with bidentate Sulphur donor borate ligands. • Highly cytotoxic Cu(II) complexes. • Metal complexes interacting with the minor groove of DNA based on Molecular docking studies. • DNA interaction and genotoxicity studies of metal complexes. The salt metathesis reaction of sodium precursors, Na[H 2 B(mb) 2 ] (Hmb = 2-mercapto-benzimidazole) and Na[H 2 B(mbt) 2 ] (Hmbt = 2-mercapto-benzothiazole) of bipodal scorpionate ligands with Cu(OAc) 2 , CoCl 2 and NiBr 2 afforded six metal complexes, 1 – 6. The metal complexes were characterized using a combination of HR ESI-MS spectrometry, elemental analysis and IR spectroscopy. The cytotoxicity effect of these complexes was assessed on three human cancerous cell lines: MCF-7 (breast carcinoma), A549 (lung carcinoma) and SW1116 (colon adenocarcinoma) and compared with that for cis -platin. Our results indicated that all complexes had desirable antitumor activities (<100 µM). Copper complexes, 1 and 4 , exhibited the highest anti-proliferative activity on all investigated cell lines, which are more effective than Ni and Co containing complexes and even cis -platin. The complex 1 also showed genotoxic effect and could effectively induce apoptosis in tumor cells. Molecular docking simulation studies on the synthesized complexes confirmed that 1 had the highest DNA-binding energy as their proposed targets, as well. [ABSTRACT FROM AUTHOR]