Serum CXCL8 and Its Specific Receptor (CXCR2) in Gastric Cancer

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. This malignancy is usually diagnosed at an advanced stage. Therefore, novel biomarkers useful in the early detection of GC are sorely needed. Some authors suggest the role of chemokines and their specific receptors in GC pathogenesis. The aim of the study was to investigate whether serum CXCL8 and its receptor (CXCR2) might be considered as potential candidates for biomarkers in the diagnosis and prognosis of GC. The study included 98 subjects: 64 GC patients and 34 healthy volunteers. CXCL8 and CXCR2 concentrations were assessed by the enzyme-linked immunosorbent assay (ELISA) method. Serum CXCL8 and CXCR2 concentrations were significantly higher in GC patients than in healthy controls, similar to the well-established tumor marker (CA19-9) and marker of inflammation (CRP). Diagnostic sensitivity of CXCL8 was the highest among all proteins tested and increased for the combined assessment with CA19-9. The area under the ROC curve for CXCL8 was higher than those for CXCR2 and classical tumor markers. Serum CXCL8 levels were indicated as a significant risk factor of GC occurrence. Our findings suggest that serum CXCL8 is a promising candidate for a biomarker in GC diagnosis and might be used as a significant predictor of GC risk.

Estrogens and the Schrödinger’s Cat in the Ovarian Tumor Microenvironment

Ovarian cancer is a heterogeneous disease affecting the aging ovary, in concert with a complex network of cells and signals, together representing the ovarian tumor microenvironment. As in the “Schrödinger’s cat” thought experiment, the context-dependent constituents of the—by the time of diagnosis—well-established tumor microenvironment may display a tumor‑protective and ‑destructive role. Systemic and locally synthesized estrogens contribute to the formation of a pro-tumoral microenvironment that enables the sustained tumor growth, invasion and metastasis. Here we focus on the estrogen biosynthetic and metabolic pathways in ovarian cancer and elaborate their actions on phenotypically plastic, estrogen-responsive, aging immune cells of the tumor microenvironment, altogether highlighting the multicomponent-connectedness and complexity of cancer, and contributing to a broader understanding of the ovarian cancer biology.

Clinical significance of serum mir-21,ca153 and cea in breast cancer

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: The serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P<0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Assessing Determinants of the Current Account Deficit: A case study of India

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: the serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P<0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress

Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7’s role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.

A vaccine for photodynamic immunogenic cell death: tumor cell caged by cellular disulfide–thiol exchange for immunotherapy

Tumor cells, caged by the protein shell, are mediated to an immunogenic cell death and transformed into a hot cell vaccine. Such vaccine protects 75% pre-immunized mice against tumor initiation and significantly retards the established tumor growth.

A distinct role for recombination repair factors in an early cellular response to transcription–replication conflicts

Transcription–replication (T–R) conflicts are profound threats to genome integrity. However, whilst much is known about the existence of T–R conflicts, our understanding of the genetic and temporal nature of how cells respond to them is poorly established. Here, we address this by characterizing the early cellular response to transient T–R conflicts (TRe). This response specifically requires the DNA recombination repair proteins BLM and BRCA2 as well as a non-canonical monoubiquitylation-independent function of FANCD2. A hallmark of the TRe response is the rapid co-localization of these three DNA repair factors at sites of T–R collisions. We find that the TRe response relies on basal activity of the ATR kinase, yet it does not lead to hyperactivation of this key checkpoint protein. Furthermore, specific abrogation of the TRe response leads to DNA damage in mitosis, and promotes chromosome instability and cell death. Collectively our findings identify a new role for these well-established tumor suppressor proteins at an early stage of the cellular response to conflicts between DNA transcription and replication.

SCIDOT-01. NANOPARTICLE DELIVERY OF MIRNAS TO INHIBIT GBM STEM CELLS

Options for treating high-grade brain tumors remain limited. Recent developments in nanomedicine provide new and exciting opportunities to treat and manage brain tumors. Epigenetic modifications, involving deregulation of non-coding RNAs, in particular miRNAs, are emerging as critical determinants of gene expression and essential drivers of neoplastic phenotypes. Cationic polymers are a class of biomaterials with great promise for targeted molecular therapeutics. We combined this cutting-edge technology with our newly discovered stem cell inhibiting miRNAs to develop nano/miR to treat gliomas. We show these nano/miR distribute throughout an established tumor in vivo, and more importantly, delivering these tumor-suppressing miRNAs using PBAE polymers inhibits the growth of established GBM tumor in mouse models. Our findings demonstrate that identifying and validating stem cell-inhibitory in combination with current advances in nanomedicine will undoubtedly impact the development of novel therapies for targeting the CSC population and treating GBM.

Spatial oxidation of L-plastin downmodulates actin-based functions of tumor cells

Several antitumor therapies work by increasing reactive oxygen species (ROS) within the tumor micromilieu. Here, we reveal that L-plastin (LPL), an established tumor marker, is reversibly regulated by ROS-induced thiol oxidation on Cys101, which forms a disulfide bridge with Cys42. LPL reduction is mediated by the Thioredoxin1 (TRX1) system, as shown by TRX1 trapping, TRX1 knockdown and blockade of Thioredoxin1 reductase (TRXR1) with auranofin. LPL oxidation diminishes its actin-bundling capacity. Ratiometric imaging using an LPL-roGFP-Orp1 fusion protein and a dimedone-based proximity ligation assay (PLA) reveal that LPL oxidation occurs primarily in actin-based cellular extrusions and strongly inhibits cell spreading and filopodial extension formation in tumor cells. This effect is accompanied by decreased tumor cell migration, invasion and extracellular matrix (ECM) degradation. Since LPL oxidation occurs following treatment of tumors with auranofin or γ-irradiation, it may be a molecular mechanism contributing to the effectiveness of tumor treatment with redox-altering therapies.