Noncoding RNAs in Lung Cancer Angiogenesis

Lung cancer is the major death-related cancer in both men and women, due to late diagnostic and limited treatment efficacy. The angiogenic process that is responsible for the support of tumor progression and metastasis represents one of the main hallmarks of cancer. The role of VEGF signaling in angiogenesis is well‐established, and we summarize the role of semaphorins and their related receptors or hypoxia‐related factors role as prone of tumor microenvironment in angiogenic mechanisms. Newly, noncoding RNA transcripts (ncRNA) were identified to have vital functions in miscellaneous biological processes, including lung cancer angiogenesis. Therefore, due to their capacity to regulate almost all molecular pathways related with altered key genes, including those involved in angiogenesis and its microenvironment, ncRNAs can serve as diagnosis and prognosis markers or therapeutic targets. We intend to summarize the latest progress in the field of ncRNAs in lung cancer and their relation with hypoxia‐related factors and angiogenic genes, with a particular focus on ncRNAs relation to semaphorins

Primary Central Nervous System Lymphoma

Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy

Parasitaemia and haematological changes in malaria-infected refugees in South Africa

Background. Haematological changes associated with malaria are well recognised, but may vary with level of malaria endemicity and patient background, haemoglobinopathy, nutritional status, demographic factors and malaria immunity. Although malaria in South Africa (SA) has been reduced dramatically in endemic areas, little is known about the haematological changes associated with malaria infection among refugee populations who live in SA cities.Objective. To describe haematological alterations among malaria-infected refugees living in Durban, SA.Methods. A cross-sectional study was conducted from September 2012 to July 2013 inclusive at a refugee centre in central Durban. Blood samples from 102 adult black African refugees were examined for infection with malaria parasites, and haematological profiles were compared with standard normal values.Results. Malaria infection was detected in 16 (15.7%) of the 102 participants. The mean haemoglobin (Hb) value was reduced (mean 9.2 g/dL) in the participants with malaria, who also had an extremely low mean packed cell volume (PCV) of 28.3%. The mean Hb value in the non-malaria-infected participants was normal (12.6 g/dL), and the mean PCV was slightly low (38.0%).Conclusions. Anaemia was more common among participants with malaria infection than among those who were uninfected. Other haematological changes were common in both infected and uninfected participants, suggesting that infections other than malaria, or other underlying factors that cause haematological alterations, may be present. This research needs to be expanded to include a large sample and other areas and infections

Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma

Hepatocellular carcinoma is difficult to treat, primarily because the underlying molecular mechanisms driving clinical outcome are still poorly understood. Growing evidence suggests that the tissue microenvironment has a role in the biological behavior of the tumor. The main clinical issue is to identify the best target for therapeutic approaches. Here, we discuss the hypothesis that the entire tissue microenvironment might be considered as a biological target. However, the tissue microenvironment consists of several cellular and biochemical components, each of which displays a distinct biological activity. We discuss the major components of this environment and consider how they may interact to promote tumor/host crosstalk

The Impact of Economic Freedom, Business Regulation and Corruption on Bank Profitability and Bank Stability: Evidence from Europe

This paper examines the impact of economic freedom, regulation, corruption and transparency on bank profitability and bank stability using a sample of 681 European financial institutions in 33 European countries over the period 2000-2012. Using unbalanced panel data and 2SLS estimation, our results show that bank performance and bank stability are negatively related, but economic freedom, regulation, corruption and transparency tend to have mixed effects at the aggregate level depending on the profitability and stability measures used. More noticeable differential effects can be detected when we disaggregate the data between the Eurozone, the non-euro European Union (EU) countries and the EU candidate countries, the size of financial institutions, the level of country income, the timing of entrance into the EU enlargement process and specialization of the banks. Our results suggest that policies promoting greater economic freedom, reducing regulation, reducing corruption and enhancing transparency need to be more targeted to reflect the diversity of the banking sector in Europe

Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde of Molecular Hematology

Chronic myelogenous leukemia (CML) is a malignancy of the myeloid cell lineage characterized by a recurrent chromosomal abnormality: the Philadelphia chromosome, which results from the reciprocal translocation of the chromosomes 9 and 22. The Philadelphia chromosome contains a fusion gene called BCR-ABL1. The BCR-ABL1 codes for an aberrantly functioning tyrosine kinase that drives the malignant proliferation of the founding clone. The advent of tyrosine kinase inhibitors (TKI) represents a landmark in the treatment of CML, that has led to tremendous improvement in the remission and survival rates. Since the introduction of imatinib, the first TKI, several other TKI have been approved that further broadened the arsenal against CML. Patients treated with TKIs require sensitive monitoring of BCR-ABL1 transcripts with quantitative real-time polymerase chain reaction (qRT-PCT), which has become an essential part of managing patients with CML. In this review, we discuss the importance of the BCR-ABL1 assay, and we highlight the growing importance of BCR-ABL1 dynamics. We also introduce a mathematical correction for the BCR-ABL1 assay that could help homogenizing the use of the ABL1 as a control gene. Finally, we discuss the growing body of evidence concerning treatment-free remission. Along with the continuous improvement in the therapeutic arsenal against CML, the molecular monitoring of CML represents the avant-garde in the struggle to make CML a curable disease

Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation

A series of cytotoxic titanocene derivatives have been immobilized onto nanostructured silica-based materials using two different synthetic routes, namely, (i) a simple grafting protocol via protonolysis of the Ti-Cl bond; and (ii) a tethering method by elimination of ethanol using triethoxysilyl moieties of thiolato ligands attached to titanium. The resulting nanostructured systems have been characterized by different techniques such as XRD, XRF, DR-UV, BET, SEM, and TEM, observing the incorporation of the titanocene derivatives onto the nanostructured silica and slight changes in the textural features of the materials after functionalization with the metallodrugs. A complete biological study has been carried out using the synthesized materials exhibiting moderate cytotoxicity in vitro against three human hepatic carcinoma (HepG2, SK-Hep-1, Hep3B) and three human colon carcinomas (DLD-1, HT-29, COLO320) and very low cytotoxicity against normal cell lines. In addition, the cells' metabolic activity was modified by a 24-h exposure in a dose-dependent manner. Despite not having a significant effect on TNFα or the proinflammatory interleukin 1α secretion, the materials strongly modulated tumor necrosis factor (TNF) signaling, even at sub-cytotoxic concentrations. This is achieved mainly by upregulation of the TNFR1 receptor production, something which has not previously been observed for these systems.We gratefully acknowledge financial support from FEDER and the Ministerio de Economía y Competitividad, Spain (grant no. CTQ2015-66164-R) and the Romanian UEFISCDI Exploratory Research Project PN-III-P4-ID-PCE-2016-0870, IMPRESS.We would also like to thank Universidad Rey Juan Carlos and Banco de Santander for supporting our Research Group of Excellence QUINANOAP. Finally, we thank D. Pérez for valuable discussion and S. Carralero and C. Forcé for their assistance with solid-state NMR experiments

Molecular profiling and the TP53 gene in diffuse large B-cell lymphoma

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Limfom difuz cu celule B mari reprezintă o neoplazie eterogenă compusă din mai multe entități biologice distincte. Mai multe studii moleculare au încercat să identifice factori prognostici și ținte de tratament potențiale. Rolul genei TP53, adesea alterată în multe malignități umane, rămâne controversat. Scopul studiului. Evaluarea progreselor actuale în subtipizarea a limfomului difuz cu celule B mari și analiza rolului patogenic și prognostic al alterărilor TP53. Material și metode. Analiza a articolelor relevante din baze de date: PubMed/MEDLINE, Cochrane Library, Web of Science. Rezultate. Mutațiile TP53 reprezintă un factor independent pentru prognostic nefavorabil și supraviețuire inferioară în limfom, cu o prevalență de aproximativ 20-25%. A fost demonstrată o îmbunătățire generală a efectului clinic și a supraviețuirii, dar nici adăugarea de rituximab, nici regimurile de chimioterapie intensificată nu au reușit să depășească efectele adverse ale mutațiilor TP53. Parametrii clinici, cum ar fi scorurile prognostice și stadiul, nu au fost asociate cu prezența alterărilor TP53. Perspectivele de tratament în cazurile cu mutații TP53 includ acționarea asupra receptorului de celulă B prin intermediul BTK și SYK, inhibiția căilor BCL2 și AKT și terapia cu celule CAR T, printre altele. Concluzii. Statutul mutațional TP53 în limfomul difuz cu celule B mari nu influențează în prezent conduita pacientului. Studii de validare suplimentare și explorarea unor abordări alternative de tratament care vizează TP53 și alte căi moleculare sunt necesare pentru a îmbunătăți rezultatele în acest subgrup.Background. Diffuse large B-cell lymphoma is a heterogeneous tumor comprised of several distinct biological entities. Multiple molecular studies have attempted to identify potential prognostic factors and treatments targets. The role of TP53, a gene often mutated in many human malignancies, remains controversial. Objective of the study. Evaluation of the current advances in subtyping of diffuse large B-cell lymphoma and analysis of the pathogenetic and prognostic role of TP53 alterations. Material and methods. Review of relevant articles in the following databases: PubMed/MEDLINE, Cochrane Library, Web of Science. Results. TP53 mutations were shown to be an independent factor for negative outcomes and inferior survival in lymphoma, with an overall prevalence of around 20-25%. An overall improvement in outcome and survival has been shown, but neither the addition of rituximab, nor the intensified chemotherapy regimens were able to overcome the adverse effects of TP53 mutations. Clinical parameters, such as prognostic scores and stage, did not seem to be associated with TP53 alterations. Potential treatment prospects in TP53-mutated cases included targeting the B-cell receptor through BTK and SYK, inhibition of BCL2 and AKT pathways, and CAR T therapy, among others. Conclusions. The mutational status of TP53 in diffuse large B-cell lymphoma does not currently influence patient management. Further validation studies and exploration of alternative treatment approaches targeting TP53 and other molecular pathways are necessary to improve clinical outcomes in this patient group