21 research outputs found
Double inferior vena cava-an important anatomical variant in retroperitoneal surgery
University of
Granada/CBU
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
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
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
Systematic Review Nanomedicine and Hyperthermia for the Treatment of Gastrointestinal Cancer: A Systematic Review
The incidence of gastrointestinal cancers has increased in recent years. Current treatments
present numerous challenges, including drug resistance, non-specificity, and severe side effects,
needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic
nanoparticles, which have gained considerable interest due to their ability to generate heat in
tumor regions upon the application of an external alternating magnetic field, a process known as
hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in
the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating
gastrointestinal cancers. After applying various inclusion and exclusion criteria (studies in the last
10 years where hyperthermia using alternative magnetic field is applied), a total of 40 articles were
analyzed. The results revealed that iron oxide is the preferred material for magnetism generation
in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly,
novel therapies employing nanoparticles loaded with chemotherapeutic drugs in combination with
magnetic hyperthermia demonstrated an excellent antitumor effect. In conclusion, hyperthermia
treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment
of gastrointestinal cancers, offering advantages over traditional therapiesPI19/01478 and PMPTA22/00136 (Instituto de Salud
Carlos III) (FEDER)Project P20_00540, A-CTS-666-UGR20B-CTS-122-UGR20 and PYC20 RE 035 (Proyectos I + D + i Junta de Andalucía 2020) (FEDER)FP-PRE grant (2021) from the Junta de Andalucia (Spain
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
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)
Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review
Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood
cancers. They exhibit a high tendency to develop early metastases and are often resistant to available
treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have
been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and
prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze
the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete
cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021
was retrieved from different databases, of which 35 articles were included for analysis. The studies
demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques
used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the
identification of CSC markers in sarcomas may facilitate the development of personalized medicine
and improve treatment outcomes.CTS-107 (Andalusian Government
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)
Differential chemotherapeutic regimen cytotoxicity against pancreatic cancer stem cells: a preliminary in vitro study
We are grateful to Scientific Instrumentation Center (CIC) from the Granada University.Introducción: El tratamiento del cáncer de páncreas en estadios avanzados se basa en diferentes regímenes de
quimioterapia. Las células madre cancerosas son responsables de la quimiorresistencia tumoral y la recurrencia
tras tratamientos en etapa adyuvante y metastásica. El objetivo de este artículo fue evaluar cómo estos regímenes
quimioterapéuticos afectan a la proporción de células madre cancerosas y la expresión de sus marcadores.
Método: Utilizamos la línea celular de adenocarcinoma pancreático PANC-1 como modelo para aplicar diferentes
protocolos quimioterapéuticos (monoterapia y terapia combinada) utilizando 5-Fluorouracilo, Oxaliplatino, Irino tecán, Gemcitabina y Abraxane.
Resultados: Tras analizar mediante RT-qPCR diferentes marcadores de células madre tumorales (SOX2, OCT4,
CD133, CD44 y CD24) en células de cáncer de páncreas tratadas con diferentes protocolos quimioterapéuticos, el
Oxaliplatino y la Gemcitabina en monoterapia fueron los quimioterápicos que seleccionaron en mayor medida las
células madre cancerosas mientras que el protocolo FOLFIRI las disminuyó.
Conclusiones: En cuanto a la selección de marcadores, ha sido mucho mayor en el caso de Gemcitabina en
monoterapia. En conclusión, estos hallazgos podrían mejorar y personalizar la terapia del cáncer de páncreas.Introduction: Pancreatic cancer treatment in advanced stages is based on different chemotherapy regimens. Can cer stem cells are responsible for tumor chemoresistance and recurrence in adjuvant and metastatic settings. The
objective of this article was to evaluate how these chemotherapeutic regimens affect the proportion of cancer stem
cells and the expression of stemness markers.
Method: We used the pancreatic adenocarcinoma cell line PANC-1 as a model to apply different chemotherapeu tic protocols (monotherapy and combined therapy) using 5-Fluorouracil, Oxaliplatin, Irinotecan, Gemcitabine and
Abraxane.
Results: After analyzing different tumor stem cell markers (SOX2, OCT4, CD133, CD44 and CD24) in pancreatic can cer cells treated with different chemotherapeutic protocols by means of RT-qPCR, Oxaliplatin and Gemcitabine in
monotherapy were the chemotherapies that selected the most cancer stem cells while the FOLFIRI protocol de creased them.
Conclusions: Regarding the selection of markers, it has been much higher in the case of Gemcitabine alone. In
conclusion, these findings could improve and personalize pancreatic cancer therapy.This work was supported by funds from group CTS-107 (Andalusian Government). F. J. Q. acknowledges the FPU2019
grant from the Ministerio de Educacion Ciencia y Deporte y Competitividad (Spain)