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Background and Objectives: High-grade malignant neuroendocrine tumors (G3 NETs) and neuroendocrine carcinomas (NECs) are characterized by rapid proliferation, high metastatic capacity, and strong expression of somatostatin receptors (SSTRs). We aimed to analyze the presence of SSTRs in NET G3 and NEC, and to correlate their expression with the use of octreotide and pasireotide. Materials and Methods: For this purpose, we first performed a retrospective study of G3 NET and NEC patients, which included the determination of SSTR expression and response to octreotide treatment. Second, we selected the H69 small cell lung cancer cell line to determine the effect of octreotide and pasireotide. Results: Our results showed the traditional somatostatin analog (SSA) octreotide was ineffective in patients with NET G3 and NEC. On the other hand, RT-qPCR showed a high expression of SSTR2 and SSTR5 in H69 cells. Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. Conclusions: In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.
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Tumores Neuroendócrinos , Octreotida , Receptores de Somatostatina , Somatostatina , Humanos , Octreotida/uso terapêutico , Octreotida/farmacologia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Somatostatina/farmacologia , Tumores Neuroendócrinos/tratamento farmacológico , Receptores de Somatostatina/análise , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
INTRODUCTION: Gastric cancer is one of the cancers most associated with thromboembolic phenomena. The objective of this article is to study if there is a correlation between thromboembolic phenomena in gastric cancer and tumor expression of PDL-1. METHODS: To this end, the association between thromboembolic events and PDL-1 expression was retrospectively studied in a sample of 46 patients from our hospital. RESULTS: The results obtained revealed a statistically significant difference between the percentage of thromboembolic events between positive and negative PDL-1 with an increase in the latter with a P value of 0.034. CONCLUSION: In conclusion, the expression of PDL-1, and with it, of an inhibitory factor of the cellular immune response, correlates with a decrease in thromboembolic events in patients with gastric cancer, which could indicate the crucial role of the immune response in which thromboembolic events occur.
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Antígeno B7-H1 , Neoplasias Gástricas , Trombose Venosa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Incidência , Estudos Retrospectivos , Neoplasias Gástricas/imunologia , Trombose Venosa/etiologia , Trombose Venosa/epidemiologiaRESUMO
The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.
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Neoplasias Experimentais , Animais , Embrião de Galinha , Humanos , Bioensaio , Membrana Corioalantoide , Medicina de PrecisãoAssuntos
Dissecação , Veia Cava Inferior , Humanos , Veia Cava Inferior/cirurgia , Espaço Retroperitoneal , AbdomeRESUMO
SUMMARY: Telocytes are a cell population described in 2011 with a multitude of functions such as tissue support, regulation of stem cell niches or intercellular signal transmission. However, there are no studies about their embryonic origin, their function in development, or their moment of appearance. The objective of this work is to try to answer these questions through histological and immunofluorescence studies with samples from the embryological collection of the Department of Anatomy of the University of Granada. In the results obtained, as demonstrated by immunofluorescence for CD34, the presence of these cells can be seen in the fourth week of embryonic development in the perinotochordal region. Its presence is evident from the sixth week of development in a multitude of organs such as the heart, skeletal muscle tissue and supporting tissue of various organs such as the kidney, brain or pericardium. Its function seems to be when the embryonic histological images are analyzed in an evolutionary way, to act as a scaffold or scaffold for the subsequent population by mature tissue elements. In conclusion, telocytes appear at a very early stage of embryonic development and would have a fundamental role in it as scaffolding and directors of organ and tissue growth.
Los telocitos son una población celular descrita en 2011 con multitud de funciones como el sostén tisular, la regulación de los nichos de células madre o la transmisión de señales intercelulares. Sin embargo, no existen estudios acerca del origen embrionario de los mismos, su función en el desarrollo ni su momento de aparición. El objetivo de este trabajo es tratar de responder a estos interrogantes mediante estudios histológicos y por inmunofluorescencia con muestras de la colección embriológica del Departamento de Anatomía de la Universidad de Granada. En los resultados se puede observar como se demuestra mediante inmunofluorescencia para CD34, la presencia de estas células en la cuarta semana del desarrollo embrionario en la región perinotocordal. Su presencia se evidencia a partir de la sexta semana del desarrollo en multitud de órganos como corazón, tejidos músculo esqueléticos y tejidos de sostén de diversos órganos como riñón, encéfalo o pericardio. Su función parece ser al ser analizadas las imágenes histológicas embrionarias de forma evolutiva, la de actuar como un andamiaje o scafold para el posterior poblamiento por elementos tisulares maduros. Como conclusión, los telocitos aparecen en un momento muy precoz del desarrollo embrionario y presentarían una función fundamental en el mismo como andamiajes y directores del crecimiento de los órganos y tejidos.
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Humanos , Telócitos/metabolismo , Telócitos/ultraestrutura , Imunofluorescência , Antígenos CD34RESUMO
Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.
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Neoplasias Colorretais , Anêmonas-do-Mar , Animais , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cromatografia , Neoplasias Colorretais/tratamento farmacológicoRESUMO
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.
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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.
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Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Ácido Valproico , Levetiracetam/farmacologia , Metotrimeprazina/farmacologia , Metotrimeprazina/uso terapêutico , Haloperidol , Biperideno/farmacologia , Biperideno/uso terapêutico , Dextrometorfano/farmacologia , Dextrometorfano/uso terapêutico , Cloridrato de Fingolimode , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , ApoptoseRESUMO
The emergence of resistance to pancreatic cancer (PC) current treatment requires the development of new therapeutic strategies. In this context, bioactive molecules from plant extracts have shown excellent properties to improve classical therapy against this type of tumor. This systematic review aims to collect all the in vitro studies related to the antiproliferative activity of isolated plant molecules that support their applicability in PC. A total of 620 articles published in the last 10 years were identified, although only 28 were finally included to meet the inclusion criteria. Our results reflect the most important biomolecules from natural compounds that induce cell death in PC and their essential mechanism of cell death, including apoptosis, pathways activated by the KRAS mutation and cycle cell arrest, among others. These in vitro studies provide an excellent molecule guide showing applications against PC and that should be tested in vivo and in clinical trials to determine their usefulness to reduce PC incidence and to improve the prognosis of these patients. However, natural compounds are isolated in small amounts, which prevents comprehensive drug screening, being necessary the role of organic synthesis for the total synthesis of natural compounds or for the synthesis of their simplified and bioactive analogs.
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Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products.
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Produtos Biológicos , Anidrases Carbônicas , Neoplasias do Colo , Euphorbia , Nanopartículas , Humanos , Camundongos , Animais , Antioxidantes , Neoplasias do Colo/tratamento farmacológico , Cumarínicos , Fosfatos de CálcioRESUMO
Continuous improvements in morphological and histochemical analyses of Apis mellifera could improve our understanding of the anatomy and physiology of these insects at both the cellular and tissue level. In this work, two different approaches have been performed to add new data on the abdomen of worker bees: (i) Micro-computed tomography (Micro-CT), which allows the identification of small-scale structures (micrometers) with adequate/optimal resolution and avoids sample damage and, (ii) histochemical multi-staining with Periodic Acid-Schiff-Alcian blue, Lactophenol-Saphranin O and pentachrome staining to precisely characterize the histological structures of the midgut and hindgut. Micro-CT allowed high-resolution imaging of anatomical structures of the honeybee abdomen with particular emphasis on the proventriculus and pyloric valves, as well as the connection of the sting apparatus with the terminal abdominal ganglia. Furthermore, the histochemical analyses have allowed for the first-time description of ventricular telocytes in honeybees, a cell type located underneath the midgut epithelium characterized by thin and long cytoplasmic projections called telopodes. Overall, the analysis of these images could help the detailed anatomical description of the cryptic structures of honeybees and also the characterization of changes due to abiotic or biotic stress conditions.
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Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.
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Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.
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Síndrome de Heterotaxia/diagnóstico , Baço/anormalidades , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia Adjuvante , Meios de Contraste/administração & dosagem , Feminino , Humanos , Achados Incidentais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Mastectomia Segmentar , Pessoa de Meia-Idade , Baço/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Pancreatic ductal adenocarcinoma (PDA) has one of the worst prognosis and higher mortality among most cancers. The diagnosis of PDA is frequently delayed due to a lack of specific biomarkers, and the efficacy of current chemotherapeutic drugs is limited. Moreover, chemotherapy is generally applied in advanced stages, where metastatic spread has already occurred. Nanotechnologybased systems are allowing to advance in the diagnosis and treatment of PDA. New nanoformulations have shown to improve the activity of conventional chemotherapeutic agents, such as gemcitabine, and new antitumor drugs, protecting them from degradation, improving their selectivity, solubility and bioavailability, and reducing their side effects. Moreover, the design of nanocarriers represents a new way to overcome drug resistance, which requires a comprehensive understanding of the tumor microenvironment of PDA. This article reviews the current perspectives, based on nanomedicine, to address the limitations of pancreatic cancer treatment, and the futures lines of research to progress in the control of this disease.
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Carcinoma Ductal Pancreático/tratamento farmacológico , Nanomedicina , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Carcinoma Ductal Pancreático/etiologia , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pancreáticas/etiologiaRESUMO
Pneumocystis jirovecii pneumonia is a very uncommon complication in lung cancer patients. We report the case of a 59-year-old, Stage IIIB non-small cell lung cancer (epidermoid) patient who was receiving concurrent chemotherapy scheme (cisplatin + vinorelbine) and radiotherapy and developed fever and dyspnea not controlled with classical antibiotics. The patient developed respiratory distress. A high-resolution computed tomography showed a crazy-paving pattern, and a bronchoalveolar lavage confirmed the diagnosis of Pneumocystis jirovecii pneumonia. The patient was successfully managed with intravenous trimethoprim/sulfamethoxazole and voriconazole. Few such cases have been reported in the literature, and in most cases, the infection has been found to be associated with aggressive oncological treatments. Therefore, Pneumocystis jirovecii pneumonia should be considered in lung cancer patients with its presenting symptoms, especially if the patient is undergoing aggressive chemotherapy and/or radiotherapy.
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Aims: To analyze the clinical relevance of O6-methylguanine-DNA methyltransferase in rectal adenocarcinoma treated with chemoradiotherapy followed by surgery. Methods: Tissue samples from 29 rectal adenocarcinoma patients were obtained after chemoradiotherapy. O6-methylguanine-DNA methyltransferase promoter methylation status was established by methylation-specific polymerase chain reaction. O6-methylguanine-DNA methyltransferase protein levels were determined by immunohistochemistry. Clinicopathologic variables, including treatment regression grade, recurrence, lymph node invasion, and stage and differentiation grade of the tumor, were determined. Results: The O6-methylguanine-DNA methyltransferase gene promoter was methylated in 81.5% of samples. Most patients (88.9%) showed low O6-methylguanine-DNA methyltransferase protein expression. O6-methylguanine-DNA methyltransferase methylation status was not correlated with any of the clinicopathological variables determined in rectal adenocarcinomas selected for chemoradiotherapy. Conclusion: O6-methylguanine-DNA methyltransferase methylation status is not correlated with clinicopathologic variables examined in rectal adenocarcinoma selected for chemoradiotherapy, although its role as a biomarker awaits further investigation.