DataSheet1_Electrophysiological and morphological modulation of neuronal-glial network by breast cancer and nontumorigenic mammary cell conditioned medium.docx

Breast cancer is a significant global health concern, with the overexpression of human epidermal growth factor receptor 2 (HER2/ERBB2) being a driver oncogene in 20%–30% of cases. Indeed, HER2/ERBB2 plays a crucial role in regulating cell growth, differentiation, and survival via a complex signaling network. Overexpression of HER2/ERBB2 is associated with more aggressive behavior and increased risk of brain metastases, which remains a significant clinical challenge for treatment. Recent research has highlighted the role of breast cancer secretomes in promoting tumor progression, including excessive proliferation, immune invasion, and resistance to anti-cancer therapy, and their potential as cancer biomarkers. In this study, we investigated the impact of ERBB2+ breast cancer SKBR-3 cell line compared with MCF10-A mammary non-tumorigenic cell conditioned medium on the electrophysiological activity and morphology of neural networks derived from neurons differentiated from human induced pluripotent stem cells. Our findings provide evidence of active modulation of neuronal-glial networks by SKBR-3 and MCF10-A conditioned medium. These results provide insights into the complex interactions between breast cancer cells and the surrounding microenvironment. Further research is necessary to identify the specific factors within breast cancer conditioned medium that mediate these effects and to develop targeted therapies that disrupt this interaction.</p

Age distribution, tobacco smoke habit and DNA ploidy status in oral potentially malignant disordes (OPMDs) and oral squamous cell carcinomas (OSCCs) patients.

<p>The bottom and the top of each box show the first and third quartile while the line inside the box represents the median (second quartile). The tips of the whiskers represent the minimum and the maximum data value. The number of patients for each category is indicated at the bottom of the corresponding box. The boxes corresponding to DNA diploid OPMDs/OSCCs are white while those corresponding to DNA aneuploid OPMDs/OSCCs have a striped pattern. Significant (MW test) P-values (P < 0.05) are indicated. The FDR q-value method was applied for multiple testing (n = 8) correction and the resulting q-values are indicated.</p

Relationship between ploidy status, age, and smoke habit, in OPMDs^a and OSCCs^b patients.

<p>Relationship between ploidy status, age, and smoke habit, in OPMDs<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184425#t004fn001" target="_blank">^a</a> and OSCCs<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184425#t004fn002" target="_blank">^b</a> patients.</p

Mean number of genomic aberrations (MNGA) per patient and age or smoking status in oral potentially malignant disordes (OPMDs) and oral squamous cell carcinomas (OSCCs) patients.

<p>The average number of aberrations per patient is represented as gray dots superimposed over boxes. These present a thick horizontal line indicating the median number per group, and delimitate the 25^th and 75^th percentile, while whiskers show the 95% confidence interval. A) average number of aberrations per patients’ age; B) average number of aberrations per patients’ smoking habit.</p

Patients’ tobacco consumption details (54 former and 76 current smokers).

<p>Patients’ tobacco consumption details (54 former and 76 current smokers).</p

Patients’ characteristics and differences in age distribution among patient subgroups.

<p>Patients’ characteristics and differences in age distribution among patient subgroups.</p

NAC, Tiron and Trolox Impair Survival of Cell Cultures Containing Glioblastoma Tumorigenic Initiating Cells by Inhibition of Cell Cycle Progression

<div><p>Reactive oxygen species (ROS) are metabolism by-products that may act as signaling molecules to sustain tumor growth. Antioxidants have been used to impair cancer cell survival. Our goal was to determine the mechanisms involved in the response to antioxidants of a human cell culture (PT4) containing glioblastoma (GBM) tumorigenic initiating cells (TICs). ROS production in the absence or presence of N-acetyl-L-cysteine (NAC), tiron, and trolox was evaluated by flow cytometry (FCM). The effects of these antioxidants on cell survival and apoptosis were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and FCM. The biological processes modulated by these drugs were determined by oligonucleotide microarray gene expression profiling. Our results showed that NAC, tiron and trolox impaired PT4 cell survival, had minor effects on ROS levels and caused wide deregulation of cell cycle genes. Furthermore, tiron and trolox caused inhibition of cell survival in two additional cell cultures containing TICs, FO-1 and MM1, established from a melanoma and a mesothelioma patient, respectively. NAC, instead, impaired survival of the MM1 cells but not of the FO-1 cells. However, when used in combination, NAC enhanced the inhibitory effect of PLX4032 (BRAF V600E inhibitor) and Gefitinib (EGFR inhibitor), on FO-1 and PT4 cell survival. Collectively, NAC, tiron and trolox modulated gene expression and impaired the growth of cultures containing TICs primarily by inhibiting cell cycle progression.</p></div

Le Courrier

28 mai 18341834/05/28 (N148)

Additional file 6: Figure S6. of Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells

Representative DNA content histograms obtained by high resolution DNA flow cytometry from SKBR-3 and BT474 cells, top and bottom row respectively. X axes show DNA content measured as intensity of fluorescent light emitted by DNA bound DAPI at 435 nm; Y axes show number of nuclei (counts). Arrow heads indicate G0/G1 and G2/M peaks. Control treatment, Ctr; Carnosic acid treatment; CA; Trastuzumab treatment, Tz; Carnosic plus Trastuzumab treatment, CA + Tz. (TIFF 396 kb

Data_Sheet_1_New miRNA Signature Heralds Human NK Cell Subsets at Different Maturation Steps: Involvement of miR-146a-5p in the Regulation of KIR Expression.ZIP

<p>Natural killer cells are cytotoxic innate lymphoid cells that play an important role for early host defenses against infectious pathogens and surveillance against tumor. In humans, NK cells may be divided in various subsets on the basis of the relative CD56 expression and of the low-affinity FcγRIIIA CD16. In particular, the two main NK cell subsets are represented by the CD56^bright/CD16^−/dim and the CD56^dim/CD16^bright NK cells. Experimental evidences indicate that CD56^bright and CD56^dim NK cells represent different maturative stages of the NK cell developmental pathway. We identified multiple miRNAs differentially expressed in CD56^bright/CD16⁻ and CD56^dim/CD16^bright NK cells using both univariate and multivariate analyses. Among these, we found a few miRNAs with a consistent differential expression in the two NK cell subsets, and with an intermediate expression in the CD56^bright/CD16^dim NK cell subset, representing a transitional step of maturation of NK cells. These analyses allowed us to establish the existence of a miRNA signature able to efficiently discriminate the two main NK cell subsets regardless of their surface phenotype. In addition, by analyzing the putative targets of representative miRNAs we show that hsa-miR-146a-5p, may be involved in the regulation of killer Ig-like receptor (KIR) expression. These results contribute to a better understanding of the physiologic significance of miRNAs in the regulation of the development/function of human NK cells. Moreover, our results suggest that hsa-miR-146a-5p targeting, resulting in KIR down-regulation, may be exploited to generate/increment the effect of NK KIR-mismatching against HLA-class I⁺ tumor cells and thus improve the NK-mediated anti-tumor activity.</p