Experimental Tumor Induction and Evaluation of Its Treatment in the Chicken Embryo Chorioallantoic Membrane Model: A Systematic Review.

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.

Quadriceps femoris muscle: anatomical variations, population frequencies and clinical implications.

Recently, the classical anatomy of the quadriceps femoris has been questioned after the publication of various morphological variations that differ from the classical description. Therefore, it is necessary to collect information to reach an agreement on its structure. For this, a systematic review was carried out using the Web of Science, Pubmed and ProQuest scientific databases, obtaining a total of 29 papers finally included in the systematic review after being subjected to inclusion and exclusion criteria. The results obtained showed an important and variable prevalence of new configurations described, such as additional heads in the rectus femoris, a different origin of the vastus intermedius, various portions of the vastus lateralis, or the involvement of the vastus medialis in the patellofemoral musculature. For this reason, understanding the anatomy of the quadriceps femoris is a matter that has not yet been fully resolved, with high variability among people that must be studied prior to the application of an invasive and/or surgical procedure.

Liposomal Doxorubicin In vitro and In vivo Assays in Non-small Cell Lung Cancer: A Systematic Review.

BACKGROUND: Liposomal Doxorubicin (Doxil®) was one of the first nanoformulations approved for the treatment of solid tumors. Although there is already extensive experience in its use for different tumors, there is currently no grouped evidence of its therapeutic benefits in non-small cell lung cancer (NSCLC). A systematic review of the literature was performed on the therapeutic effectiveness and benefits of Liposomal Doxil® in NSCLC. METHODS: A total of 1022 articles were identified in publications up to 2020 (MEDLINE, Cochrane, Web of Science Core Collection and Scopus). After applying inclusion criteria, the number was restricted to 114, of which 48 assays, including in vitro (n=20) and in vivo (animals, n=35 and humans, n=6) studies, were selected. RESULTS: The maximum inhibitory concentration (IC50), tumor growth inhibition rate, response and survival rates were the main indices for evaluating the efficacy and effectiveness of Liposomal DOX. These have shown clear benefits both in vitro and in vivo, improving the IC50 of free DOX or untargeted liposomes, depending on their size, administration, or targeting. CONCLUSION: Doxil® significantly reduced cellular proliferation in vitro and improved survival in vivo in both experimental animals and NSCLC patients, demonstrating optimal safety and pharmacokinetic behavior indices. Although our systematic review supports its benefits for the treatment of NSCLC, additional clinical trials with larger sample sizes are necessary to obtain more precise clinical data on its activity and effects in humans.

Improved antitumor activity through a tyramidyl maslinic acid derivative. Design and validation as drug-loaded electrospun polymeric nanofibers.

Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC.

Telocytes in Human Embryonic Development: A Preliminary Microscopic Anatomy Study / Telocitos en el Desarrollo Embrionario Humano: Un Estudio Preliminar de Anatomía Microscópica

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.

Combining Olaparib and Ascorbic Acid on Nanoparticles to Enhance the Drug Toxic Effects in Pancreatic Cancer.

Introduction: Pancreatic cancer (PC) shows a very poor response to current treatments. Development of drug resistance is one of the causes of the therapy failure, being PARP1 (poly ADP-ribose polymerase 1) a relevant protein in the resistance mechanism. In this work, we have functionalized calcium phosphate-based nanoparticles (NPs) with Olaparib (OLA, a PARP-1 inhibitor) in combination with ascorbic acid (AA), a pro-oxidative agent, to enhance their individual effects. Methods: Amorphous Calcium Phosphate (ACP) NPs were synthesized through a biomimetic approach and then functionalized with OLA and AA (NP-ACP-OLA-AA). After evaluation of the loading capacity and release kinetic, cytotoxicity, cell migration, immunofluorescence, and gene expression assays were performed using pancreatic tumor cell lines. In vivo studies were carried out on tumors derived from the PANC-1 line in NOD SCID gamma (NSG) mice. Results: NP-ACP-OLA-AA was loaded with 13%wt of OLA (75% loading efficiency) and 1% of AA, respectively. The resulting dual nanosystem exhibited a gradual release of OLA and AA, being the latter protected from degradation in solution. This ensured the simultaneous availability of OLA and AA for a longer period, at least, during the entire time of in vitro cell experiments (72 hours). In vitro studies indicated that NP-ACP-OLA-AA showed the best cytotoxic effect outperforming that of the free OLA and a higher genotoxicity and apoptosis-mediated cytotoxic effect in human pancreatic ductal adenocarcinoma cell line. Interestingly, the in vivo assays using immunosuppressed mice with PANC-1-induced tumors revealed that NP-ACP-OLA-AA produced a higher tumor volume reduction (59.1%) compared to free OLA (28.3%) and increased the mice survival. Conclusion: Calcium phosphate NPs, a highly biocompatible and biodegradable system, were an ideal vector for the OLA and AA co-treatment in PC, inducing significant therapeutic benefits relative to free OLA, including cytotoxicity, induction of apoptosis, inhibition of cell migration, tumor growth, and survival.

Evaluating Metabolite-Based Biomarkers for Early Diagnosis of Pancreatic Cancer: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms "Biomarkers, Tumor", "Pancreatic Neoplasms", "Early Diagnosis", "Metabolomics" and "Lipidome" (January 2018-March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.

Antiproliferative, Antioxidant, Chemopreventive and Antiangiogenic Potential of Chromatographic Fractions from Anemonia sulcata with and without Its Symbiont Symbiodinium in Colorectal Cancer Therapy.

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.

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 therapies.

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.

Antioxidant and Chemopreventive Activity of Protein Hydrolysates from Raw and Germinated Flour of Legumes with Commercial Interest in Colorectal Cancer.

Legumes are a highly nutritious source of plant protein, fiber, minerals and vitamins. However, they also contain several bioactive compounds with significant potential benefits for human health. The objectives of this study were to evaluate the antioxidant, antitumor and chemopreventive activity of functional extracts from legumes using raw and germinated flours of six legume species of commercial interest. The methodology carried out consisted on the development of protein hydrolysates, assessment of their antioxidant capacity and in vitro tests on T84, HCT15 and SW480 colorectal cancer (CRC) cell lines. Our results showed a high antitumor activity of protein hydrolysate from M. sativa. Likewise, when combined with 5-Fluorouracile (5-Fu), there was a synergistic effect using extract concentrations from 50 to 175 µg/mL and 5-Fu concentrations from 1.5 to 5 µM. Similarly, the induction effect on detoxifying enzymes by the extracts of M. sativa, germinated V. faba Baraca × LVzt1 and V. narbonensis, which produced a higher induction rate than the positive control sulforaphane (10 µM), should be highlighted. Therefore, incorporating these enzymes into the diet could provide nutritional effects, as well as play an effective role in cancer chemoprevention and therapy.

Active Biomolecules from Vegetable Extracts with Antitumoral Activity against Pancreas Cancer: A Systematic Review (2011-2021).

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.

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.

Antibody-Functionalized Nanoformulations for Targeted Therapy of Colorectal Cancer: A Systematic Review.

The failure of chemotherapeutic treatment in colorectal cancer (CRC), the second most mortal cancer worldwide, is associated with several drug limitations, such as non-selective distribution, short half-life, and development of multiple resistances. One of the most promising strategies in CRC therapy is the development of delivery systems based on nanomaterials that can transport antitumor agents to the tumor site more efficiently, increasing accumulation within the tumor and thus the antitumor effect. In addition to taking advantage of the increased permeability and retention effect (EPR) of solid tumors, these nanoformulations can be conjugated with monoclonal antibodies that recognize molecular markers that are specifically over-expressed on CRC cells. Active targeting of nanoformulations reduces the adverse effects associated with the cytotoxic activity of drugs in healthy tissues, which will be of interest for improving the quality of life of cancer patients in the future. This review focuses on in vitro and in vivo studies of drug delivery nanoformulations functionalized with monoclonal antibodies for targeted therapy of CRC.

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.

In Vivo Nutritional Assessment of the Microalga Nannochloropsis gaditana and Evaluation of the Antioxidant and Antiproliferative Capacity of Its Functional Extracts.

Nannochloropsis gaditana is a microalga with interesting nutritional and functional value due to its high content of protein, polyunsaturated fatty acids, and bioactive compounds. However, the hardness of its cell wall prevents accessibility to these components. This work aimed to study the effect of a treatment to increase the fragility of the cell wall on the bioavailability of its nutrients and functional compounds. The antioxidant and antiproliferative capacity of functional extracts from treated and untreated N. gaditana was assessed, and the profile of bioactive compounds was characterized. Furthermore, to study the effect of treatment on its nutrient availability and functional capacity, an in vivo experiment was carried out using a rat experimental model and a 20% dietary inclusion level of microalgae. Functional extracts from treated N. gaditana exhibited higher antioxidant activity than the untreated control. Furthermore, the treated microalga induced hypoglycemic action, higher nitrogen digestibility, and increased hepatic antioxidant activity. In conclusion, N. gaditana has interesting hepatoprotective, antioxidant, and anti-inflammatory potential, thus proving itself an ideal functional food candidate, especially if the microalga is treated to increase the fragility of its cell wall before consumption.

Differential chemotherapeutic regimen cytotoxicity against pancreatic cancer stem cells: a preliminary in vitro study / Citotoxicidad diferencial según el régimen de quimioterapia contra las células madre del cáncer de páncreas: estudio preliminar in vitro

Introduction: Pancreatic cancer treatment in advanced stages is based on different chemotherapy regimens. Cancer 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 chemotherapeutic 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 cancer 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 decreased 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. (AU)

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, Irinotecán, 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. (AU)

Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer.

Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX's mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.

In Vitro Efficacy of Extracts and Isolated Bioactive Compounds from Ascomycota Fungi in the Treatment of Colorectal Cancer: A Systematic Review.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Despite the advances and success of current treatments (e.g., chemotherapy), there are multiple serious side effects which require the development of new treatment strategies. In recent years, fungi have gained considerable attention as a source of extracts and bioactive compounds with antitumor capabilities because of their antimicrobial and antioxidant properties and even their anti-inflammatory and antiviral activities. In the present review, a systematic search of the existing literature in four electronic databases was carried out in which the antitumor activity against CRC cells of Ascomycota fungi extracts or compounds was tested. The systematical research in the four databases resulted in a total of 883 articles. After applying exclusion and inclusion criteria, a total of 75 articles were finally studied. The order Eurotiales was the most studied (46% of the articles), and the ethyl acetate extraction was the most used method (49% of the papers). Penicillium extracts and gliotoxin and acetylgliotoxin G bioactive compounds showed the highest cytotoxic activity. This review also focuses on the action mechanisms of the extracts and bioactive compounds of fungi against CRC, which were mediated by apoptosis induction and the arrest of the cell cycle, which induces a notable reduction in the CRC cell proliferation capacity, and by the reduction in cell migration that limits their ability to produce metastasis. Thus, the ability of fungi to induce the death of cancer cells through different mechanisms may be the basis for the development of new therapies that improve the current results, especially in the more advanced stages of the CCR.