Targeting CXCR4 in AML and ALL

The interaction of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts with the bone marrow microenvironment regulates self-renewal, growth signaling, as well as chemotherapy resistance. The chemokine receptor, CXC receptor 4 (CXCR4), with its ligand chemokine ligand 12 (CXCL12), plays a key role in the survival and migration of normal and malignant stem cells to the bone marrow. High expression of CXCR4 on AML and ALL blasts has been shown to be a predictor of poor prognosis for these diseases. Several small molecule inhibitors, short peptides, antibodies, and antibody drug conjugates have been developed for the purposes of more effective targeting and killing of malignant cells expressing CXCR4. In this review we will discuss recent results and strategies in targeting CXCR4 with these agents in patients with AML or ALL

Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney

Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney.BackgroundThe permanent kidney, or metanephros, develops through a complex series of reciprocal inductive events and involves branching morphogenesis, tubulogenesis, angiogenesis, and tissue remodeling. Fibroblast growth factors (FGFs) are a family of growth and differentiation factors that have been implicated in metanephric development. FGFs exert their actions through tyrosine kinase receptors, FGFRs, which are encoded by four FGFR genes (FGFR1 through FGFR4).MethodsReverse transcriptase-polymerase chain reaction was used to detect the expression of FGFs and FGFRs in rat metanephroi from embryonic day (E) 14 to E21. Nonradioactive in situ hybridization was used to localize FGF1 mRNA in E20 rat metanephroi, and immunohistochemistry was used to localize FGFRs in E15 and E20 rat metanephroi.ResultsWe detected the expression of mRNAs for FGF1 through FGF5, FGF7 through FGF10, and FGFR1 through FGFR4 (IIIb and IIIc splice variants) in rat metanephroi from E14 to E21. By in situ hybridization, FGF1 mRNA was detected in the nephrogenic zone, ureteric epithelium, and developing nephron elements. FGFR proteins were localized in a distinct pattern that altered with maturation. FGFR1 was widely distributed in developing metanephric epithelia and mesenchyme, but not in developing interstitium. FGFR2 was also widely distributed in nephron epithelia, particularly in proximal convoluted tubules, but was not detected in metanephric mesenchyme, mesenchymal condensates, or developing interstitium. FGFR3 was localized to mesenchymal condensates, nephron elements, and medullary interstitium but not proximal convoluted tubules. FGFR4 was localized mostly to maturing nephron structures and was not detected in nephrogenic mesenchyme, mesenchymal condensates, or developing interstitium.ConclusionsThese results indicate that FGFs and FGFRs are expressed in the developing rat metanephros from at least E14 and that they likely play important roles in metanephric development and maturation

Service-learning by PhD students to aid socially neglected people

In recent years, there have been calls for change in higher education to meet the needs of today's society. A higher education that enables our students to offer solutions to struggling areas of our society. Innovative and differentiating solutions from what we have been used to until now. In view of these needs, it is necessary to unite the society, which reveals its main needs, and the university community, which offers solutions on the knowledge acquired. One of the ways to carry out this integration is based on developing a methodology called "Service-Learning" (SL). This learning method is based on a strategy of collaboration between educational centers and society itself. At present, this methodology is spreading within higher education institutions worldwide. This learning strategy emerged as a learning methodology in America, to be later extended to Europe, from the United Kingdom to the rest of the continent, and from there, reaching a global impact. Throughout this long road, this methodology has been improving, encouraging the creation of increasingly strong links between educational institutions and universities, and society, by promoting the improvement of student training as well as the development of certain areas of society. This paper presents a SL project where two apparently disparate areas are related, such as doctoral students in the area of chemical engineering and sectors of society at risk of exclusion. Specifically, the objective is for the students to present some of the technological developments they have achieved to a neglected sector of society, which should participate not only in the developments, but also learning about the technical base of such technologies.This work has been carried out with the financial support of the SL UCM 2018/19_16 project and the Madrid City Council.Torrecilla, J.; Buitrón Ruiz, S.; Sánchez, M.; Cancilla, JC.; Pradana López, S.; Perez Calabuig, AM. (2020). Service-learning by PhD students to aid socially neglected people. En 6th International Conference on Higher Education Advances (HEAd'20). Editorial Universitat Politècnica de València. (30-05-2020):831-837. https://doi.org/10.4995/HEAd20.2020.11153OCS83183730-05-202

Service-learning - Diagnostic technologies presented by Ph.D. students to help socially neglected people during the SARS-CoV-2 pandemic

[EN] Innovation is becoming a fundamental part of many sectors and environments, including universities, not only regarding their research but also how education is approached. In this line, one of the ways to achieve these objectives is based on a collaboration between society, which presents a need to be solved, and the University. This society-university integration is achievable via the Service-Learning methodology (SLM), which has always been based on establishing strong links between the educational world and society. This paper presents a SLM-based project linked to technological development for the health sector during the SARS-CoV-2 pandemic. Specifically, undergraduate chemistry students, and Ph.D. students led by professors have presented part of their technological developments to people in society who are at risk of exclusion to help them understand aspects of infection as well as diagnosis of diseases. In short, the objective is to transfer in an enjoyable fashion, a set of technological developments and knowledge that can help society understand aspects related to the COVID-19 pandemic.This work has been carried out with the financial support of the SL UCM 2018/19_16 and SL UCM 2019/21_14 project and the Madrid City Council.Torrecilla, J.; Cancilla, J.; Pradana López, S.; Pérez Calabuig, A.; Izquierdo, M.; García Rodríguez, Y.; Reyes Ramirez, E.... (2021). Service-learning - Diagnostic technologies presented by Ph.D. students to help socially neglected people during the SARS-CoV-2 pandemic. En 7th International Conference on Higher Education Advances (HEAd'21). Editorial Universitat Politècnica de València. 1141-1147. https://doi.org/10.4995/HEAd21.2021.13056OCS1141114

Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath

Two of the biggest challenges in medicine today are the need to detect diseases in a noninvasive manner and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly modified silicon nanowire field effect transistor (SiNW FET) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma, and chronic obstructive pulmonary disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlate their sensitivity and selectivity toward volatile organic compounds (VOCs) linked with the various disease breathprints. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples show that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with >80% accuracy. Overall, this approach has the potential to support detection of many diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant investigations

Service-Learning at the Postgraduate Level to Reach Depressed Sectors of Society

Currently, a substantial change is being demanded from Higher Education, which should be oriented towards innovation with a much more practical approach. To obtain these objectives, the collaboration between society, which presents a need, and the University, which offers alternatives, is sought. This integration could be guided by "Service-Learning", which aims to link society with academic institutions, promoting the enrichment, not only of the host community, but also by training students. This paper presents a Service-Learning project linked to doctoral studies which present technological developments to people in society who are in danger of exclusion