Double inferior vena cava-an important anatomical variant in retroperitoneal surgery

University of Granada/CBU

Vestir los balcones. : Una propuesta de arte participativo durante el confinamiento

We would like to introduce the artistic experience Dressing Up the Balconies, a work intended for citizen’s participation that was developed during the early days of lockdown. This allowed us to remain united when sending a message of welcome and thanks for the people looking after all of us. The structure of the following text leads us to contextualise the activity by analysing the meaning of the exhibition spaces that shelter our project: windows and balconies. We continue by reasoning why this proposal was tackled with the approach of participatory art. Thus, the text puts forward some thoughts on collaborative practices and the use of handicrafts therein. The activity became a way of relating rooted in art, and each creation was a node in the net that permitted us to keep making art together.Presentamos la experiencia artística Vestir los balcones, una obra de participación ciudadana desarrollada durante los días de confinamiento que nos permitió estar unidas para lanzar un mensaje de acogida y reconocimiento a quienes nos cuidaban.  La configuración del presente texto nos lleva a contextualizar la actividad analizando el sentido del espacio expositivo que acoge nuestro proyecto: los balcones y ventanas. Damos paso a entender por qué se aborda la propuesta desde los planteamientos del arte participativo. Así, el texto, propone una reflexión en torno a las prácticas colaborativas y el uso de las manualidades que en ellas se dan. La actividad se convirtió en una forma de relación desde lo artístico siendo cada creación un nudo de la red que nos permitía seguir creando juntos.&nbsp

Synthetic Circular miR-21 Sponge as Tool for Lung Cancer Treatment

This work was funded by the CTS-107 Group. This work was also partially supported by a grant from the Instituto de Salud Carlos III (ISCIII) (project PI19/01478) (FEDER).Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we chose miR-21, which is upregulated and implicated in lung cancer. We constructed a miR-21 sponge and inserted it into a vector that facilitates circular RNA production (Circ-21) to study its effect on growth, colony formation, and migration in lung cancer cell lines and multicellular tumor spheroids (MTS). Circ-21 induced a significant and time-dependent decrease in the growth of A549 and LL2 cells, but not in L132 cells. Furthermore, A549 and LL2 cells transfected with Circ-21 showed a lower number of colonies and migration than L132. Similar findings were seen in A549 and LL2 Circ-21 MTS, which showed a significant decrease in volume growth, but not in L132 Circ-21 MTS. Based on this, the miR-21 circular sponge may suppress the processes of tumorigenesis and progression. Therefore, our system based on circular sponges seems to be effective, as a tool for the capture of other miRNAs.Instituto de Salud Carlos III European Commission PI19/01478CTS-10

PARP1 inhibition by Olaparib reduces the lethality of pancreatic cancer cells and increases their sensitivity to Gemcitabine

Pancreatic cancer (PC) is one of the tumors with the lowest survival rates due to the poor efficacy of the treatments currently used. Gemcitabine (GMZ), one of the chemotherapeutic agents employed when the tumor is unresectable, frequently fails due to the development of drug resistance. PARP1 is a relevant protein in this phenomenon and appears to be related to cancer progression in several types of tumors, including PC. To determine the relevance of PARP1 in the development and treatment of PC, we used the Panc02 cell line to generate modified PC cells with stably inhibited PARP1 expression (Panc02-L) and used GMZ, Olaparib (OLA) and GMZ+OLA as therapeutic strategies. Viability, radiosensitization, angiogenesis, migration, colony formation, TUNEL, cell cycle, multicellular tumorsphere induction and in vivo assays were performed to test the influence of PARP1 inhibition on resistance phenomena and tumor progression. We demonstrated that stable inhibition or pharmacological blockade of PARP1 using OLA-sensitized Panc02 cells against GMZ significantly decreased their IC50, reducing colony formation capacity, cell migration and vessel formation (angiogenesis) in vitro. Furthermore, in vivo analyses revealed that Panc02-L-derived (PARP1-inhibited) tumors showed less growth and lethality, and that GMZ+OLA treatment significantly reduced tumor growth. In conclusion, PARP1 inhibition, both alone and in combination with GMZ, enhances the effectiveness of this chemotherapeutic agent and represents a promising strategy for the treatment of PC.Granada University and ibs. GRANADA INB-009Instituto de Salud Carlos III European Commission DTS17/00081Junta de Andalucia (FEDER) (Spain) CTS-107 A-CTS-666UGR20 B-CTS-122-UGR20Ministerio de Educaci 'on, Ciencia y Deporte y Competitividad (Spain

Antitumor Effect of Traditional Drugs for Neurological Disorders: Preliminary Studies in Neural Tumor Cell Lines

Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood–brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood–brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood–brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.Funding for open access charge: Universidad de Granada / CBUA. This work was supported by the Project Innbio INB-009 (Granada University and ibs. GRANADA) and by the CTS-107 Group of the Junta de Andalucía (Spain)

The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among all cancer types. Its delayed diagnosis precludes curative resection, thus most of the current therapies against PDAC are based on chemo- and radiotherapy. Unfortunately, these strategies are insufficient to improve its poor prognosis. Despite the advances made in chemotherapy (e.g. nab-Paclitaxel and Gemcitabine), many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance. Currently, more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors, including different integrins, mucins, NF-κβ, RAS and CXCR4. Moreover, drug resistance in PDAC is thought to be mediated by the modulation of miRNAs (e.g. miRNA-21, miRNA-145 and miRNA-155), which regulate genes that participate in cell proliferation, invasion and metastasis. Finally, cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes -involved in drug transport-, and enzymes such as aldehyde dehydrogenases -implicated in cellular drug metabolism- and poly (ADP-ribose) polymerases -involved in drug-induced DNA damage repair-. Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.This work was funded by grants from Instituto de Salud Carlos III (Grant No. DTS15/00201 and DTS17/00081) and Junta de Andalucía (Grant No. PIN-0474-2016)

Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.CTS-107 GroupInstituto de Salud Carlos IIIEuropean Commission PI19/0147

Preventive effects of Brassicaceae family for colon cancer prevention: A focus on in vitro studies

The emergence of adverse effects and resistance to colorectal cancer (CRC) current therapies calls for the development of new strategies aimed at both preventing and treating. In this context, functional extracts from Brassicaceae family contains abundant bioactive compounds directly related to a positive effect on human health including cancer. The main objective of this systematic review is to compile all recent studies that analyzed the in vitro antiproliferative activity of functional extracts or isolated molecules from the Brassicaceae family against CRC. A total of 711 articles published between January 2011 and May 2021 were identified. Of them, 68 met our inclusion criteria. Different standardized protocols using variable parts of plants of the Brassicaceae family resulted in diverse bioactive extracts and/or compounds. Most of them were related to isothiocyanates, which showed significant antitumor activity against CRC. These in vitro studies provide an excellent guide to direct research on the applications of plants of the Brassicaceae family to the prevention of this type of tumor. The extracts and molecules with demonstrated activity against CRC should be tested in vivo and in clinical trials to determine their usefulness in the prevention of this cancer to reduce its global incidence.Spanish Government RTC2019-006870-1Junta de Andalucia P18-TP-1420Granada UniversityCELLBITEC S.L.FPU2019 grant from the Ministerio de Universidades (Spain) FPU19/06170Spanish Government DIN2018009995B04847216Andalusian Government AGR145 CTS-10

Plant-Mediated Inorganic Nanoparticles for Anti-Tumor Therapy in Colorectal Cancer: A Systematic Review

Colon cancer is the third most frequent neoplasm and the second most lethal worldwide. Despite progress in its treatment, new therapies are still needed to improve the prognosis of this type of tumor and, in this context, the use of plant compounds with anti-tumor properties has been increasing in recent years. The aim of this systematic review was to analyze the potential benefits of encapsulation of compounds derived from plant extracts in nanoparticles and their cytotoxic effect under in vitro conditions. Once the search strategy was defined based on the selected MESH terms, 147 publications published since 2012 were identified from three different databases (PubMed, SCOPUS and WOS). After eliminating duplicates and applying the inclusion and exclusion criteria, 17 studies were finally included. The results showed that the use of natural extracts encapsulated in nanoparticles offered significant cytotoxic activity against colon neoplastic cells by increasing the therapeutic effect of free plant extracts through their encapsulation and without producing toxicity on healthy cells. In addition, most studies (14) involved metal-derived nanoparticles (zinc, iron and gold). Despite the possible efficacy of these nanodrugs, more in vivo studies are needed to elucidate their potential future therapeutic application and their biocompatibilityInstituto de Salud Carlos IIIPI19/01478-FEDERPMPTA22/00136Junta de AndalucíaA-CTS-666-UGR20P20_00540B-CTS-122- UGR20Ministerio de Ciencia e Innovación (RTC2019-006870-1)FEDERCTS-107 (Andalusian Government

Plant-Derived Bioactive Compounds for Rhabdomyosarcoma Therapy In Vitro: A Systematic Review

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, constitutes approximately 40% of all recorded soft tissue tumors and is associated with a poor prognosis, with survival rates of less than 20% at 3 years. The development of resistance to cytotoxic drugs is a primary contributor to therapeutic failure. Consequently, the exploration of new therapeutic strategies is of vital importance. The potential use of plant extracts and their bioactive compounds emerges as a complementary treatment for this type of cancer. This systematic review focuses on research related to plant extracts or isolated bioactive compounds exhibiting antitumor activity against RMS cells. Literature searches were conducted in PubMed, Scopus, Cochrane, and WOS. A total of 173 articles published to date were identified, although only 40 were finally included to meet the inclusion criteria. Furthermore, many of these compounds are readily available and have reduced cytotoxicity, showing an apoptosis-mediated mechanism of action to induce tumor cell death. Interestingly, their use combined with chemotherapy or loaded with nanoparticles achieves better results by reducing toxicity and/or facilitating entry into tumor cells. Future in vivo studies will be necessary to verify the utility of these natural compounds as a therapeutic tool for RMS.Spanish Ministry of Science and Innovation (FEDER) (CPP2022-009967 and CPP2022-010017)Spanish Ministry of Universities and Science (RTC2019-006870-1