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El cáncer de cabeza y cuello es un tipo de cáncer poco frecuente cuya incidencia ha aumentado en los últimos años, afectando principalmente a hombres mayores de 50 años. Engloba varios tipos de tumores en distintas zonas, como la cavidad oral, faringe, laringe, glándulas salivares o senos paranasales. Entre los principales factores de riesgo destacan virus como el papiloma o Epstein-Barr, alcohol y tabaco. El diagnóstico se realiza mediante endoscopia, punción de ganglios o pruebas de imagen, y es necesario confirmar mediante biopsia. La mayoría de los tumores se diagnostican en estadios avanzados o metastásicos. En estas etapas aparecen síntomas como mucositis, dificultar al tragar, xerostomía o llagas en la boca. El tratamiento no farmacológico es útil sobre todo en etapas iniciales del tumor, e incluye la cirugía y radioterapia. El tratamiento farmacológico se utiliza en etapas más avanzadas o metastásicas, tanto en monoterapia como combinado con el no farmacológico, e incluye la quimioterapia, terapia dirigida e inmunoterapia. En la quimioterapia destacan el cisplatino, que se une y rompe la cadena de ADN, y el metotrexato, que es un antimetabolito del ácido fólico. La terapia dirigida incluye anticuerpos monoclonales contra el EGFR, como cetuximab, e inhibidores de la tirosina quinasa, como erlotinib y gefitinib. La reciente introducción de la inmunoterapia en este tipo de cáncer ha incrementado la supervivencia de los pacientes, e incluye anticuerpos monoclonales contra la proteína PD-1, como pembrolizumab y nivolumab. También existen nuevos medicamentos contra este tipo de cáncer, aunque aún se encuentran en fases clínicas y no se han aprobado para su uso en humanos. Sin embargo, algunos de estos están aportando resultados prometedores en quimioterapia (xevinapant), terapia dirigida (panitumumab y lenvatinib) o inmunoterapia (camrelizumab)

El glioblastoma es el tumor cerebral primario maligno más frecuente en adultos. A pesar de los avances en el tratamiento del cáncer en los últimos años, en el caso del glioblastoma continúa siendo una enfermedad incurable con una mediana de supervivencia que no supera los 15 meses. Los tratamientos actuales no son lo suficientemente eficaces para eliminar a las células cancerosas, y evitar la progresión de la patología. Este hecho queda reflejado en que únicamente el 5,5% de los pacientes sobreviven más de 5 años después del diagnóstico. Por ello, es de especial importancia la búsqueda de nuevos fármacos más eficaces para este tipo de astrocitoma. El objetivo principal de este trabajo es realizar una revisión bibliográfica de los fármacos que se encuentran en fases avanzadas de ensayos clínicos en los últimos 10 años para el tratamiento del glioblastoma. Para ello, se ha ejecutado una búsqueda bibliográfica en fuentes científicas oficiales e instituciones dedicadas al estudio de la oncología. Actualmente, el tratamiento del glioblastoma y del resto de astrocitomas se basa en la cirugía, seguida de radioterapia y terapia farmacológica, en la que destaca la utilización de quimioterapia con temozolomida en monoterapia o en combinación con otros fármacos. Los nuevos tratamientos que se hallan en ensayos clínicos se enfocan en terapia dirigida, inmunoterapia, terapia génica y dispositivos electrónicos de administración intracraneal, combinados con terapias tradicionales o en monoterapia.

Antecedentes: El Trastorno por Déficit de Atención con Hiperactividad (TDAH), es un trastorno del neurodesarrollo que afecta a las zonas del cerebro implicadas en el control de la atención, el movimiento o la conducta. Es el trastorno mental más prevalente en la infancia y puede permanecer hasta la vida adulta, afectando al rendimiento de la persona en distintos ámbitos de su vida. Objetivos: Realizar una revisión bibliográfica del tratamiento actual para el TDAH en España y de los nuevos tratamientos en ensayos clínicos. Metodología: Como fuentes bibliográficas se utilizaron bases de datos científicas como PubMed y Clinicaltrials, guías farmacoterapéuticas para el TDAH entre otras fuentes. Resultados y Discusión: El TDAH requiere un tratamiento multimodal, en el que se combina la terapia no farmacológica y el tratamiento farmacológico. El tratamiento no farmacológico se centra en mejorar la conducta del paciente mediante terapias psicológicas. Dentro del tratamiento farmacológico existen dos grupos de fármacos indicados para el TDAH, los estimulantes (metilfenidato, lisdexanetamina) y los no estimulantes (atomoxetina, guanfacina). Actualmente, se han desarrollado nuevas intervenciones farmacológicas (Qelbree®, Azstarys®), que han sido aprobadas por la FDA, pero aún no se han autorizado en Europa. Otros fármacos aún se encuentran en ensayos clínicos de fase III, pero podrían suponer una nueva alternativa para el tratamiento del TDAH, como centanafadina y NRCT-101. Junto con estos avances terapéuticos también es clave la implicación de los profesionales sanitarios en el TDAH. La farmacia comunitaria tiene un papel muy importante en el trastorno mediante el seguimiento farmacoterapéutico a estos pacientes. Conclusiones: La combinación del tratamiento farmacológico y el no farmacológico es la intervención más eficaz para el abordaje del TDAH. La falta de adherencia al tratamiento, errores en la administración o los efectos adversos pueden conducir al fracaso del tratam, Background: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects the areas of the brain involved in the control of attention, movement or behavior. It is the most prevalent mental disorder in childhood and can persist into adulthood, affecting a person's performance in different areas of their life. Objectives: Conduct a bibliographic review of the current treatment for ADHD in Spain and new treatments in clinical trials. Methodology: Bibliographic source used were scientific databases such as PubMed and Clinicaltrials, pharmacotherapeutic guidelines for ADHD, among other sources. Results and Discussion: ADHD requires multimodal treatment, in which non-pharmacological therapy and pharmacological treatment are combined. Non-pharmacological treatment focuses on improving the patient's behavior through psychological therapies. Within the pharmacological treatment there are two groups of drugs indicated for ADHD, stimulants (methylphenidate, lisdexanetamine) and non-stimulants (atomoxetine, guanfacine). Currently, new pharmacological interventions have been developed (Qelbree®, Azstarys®), which have been approved by the FDA, but have not yet been authorized in Europe. Other drugs are still in phase III clinical trials, but could represent a new alternative for the treatment of ADHD, such as centanafadine and NRCT-101. Along with these therapeutic advances, the involvement of health professionals in ADHD is also key. Community pharmacy has a very important role in the disorder through pharmacotherapeutic monitoring of these patients. Conclusions: The combination of pharmacological and non-pharmacological treatment is the most effective intervention to address ADHD. Lack of adherence to treatment, errors in administration or adverse effects can lead to treatment failure, with the community pharmacist being a key figure in detecting these problems.

Every year, cancer kills millions of people around the world. Finding more selective anticancer agents is essential to improve the low survival rates of patients with metastatic cancers. Since the research of natural products is a valuable approach to the discovery of new compounds and the Iberian flora offers a rich source of unstudied plants, we have carried out a random screening of 76 plant species from 43 families collected in Andalusia (South of Spain). Using non-malignant cells (HaCaT) and lung cancer cells (A549), we found that the extract from Arum italicum Mill. subsp. italicum (Araceae), Mandragora autumnalis Bertol. (Solanaceae), Rhamnus alaternus L. (Rhamnaceae), and Lomelosia simplex (Desf.) Raf. subsp. dentata (Jord. & Fourr.) Greuter & Burdet (Dipsacaceae) showed selective cytotoxicity against lung cancer cells. Extracts of plant species belonging to the Iridaceae family showed high selective activity against cancer cells, highlighting that the Xiphion xiphium (L.) M.B. Crespo, Mart.-Azorín & Mavrodiev flower extract was more selective against lung cancer cells than the standard anticancer drugs, cisplatin and 5-fluorouracil. This extract also showed modest selective cytotoxicity against bladder carcinoma cells (T24). The number of cells in the G1 phase increased after treatment with the extract from Xiphion xiphium. Our research indicates that various plants are potential sources for the isolation and development of new anticancer drugs.

Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53−/− cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Unscheduled R loops can be a source of genome instability, a hallmark of cancer cells. Although targeted proteomic approaches and cellular analysis of specific mutants have uncovered factors potentially involved in R-loop homeostasis, we report a more open screening of factors whose depletion causes R loops based on the ability of activation-induced cytidine deaminase (AID) to target R loops. Immunofluorescence analysis of gH2AX caused by small interfering RNAs (siRNAs) covering 3,205 protein-coding genes identifies 59 potential candidates, from which 13 are analyzed further and show a significant increase of R loops. Such candidates are enriched in factors involved in chromatin, transcription, and RNA biogenesis and other processes. A more focused study shows that the DDX47 helicase is an R-loop resolvase, whereas the MeCP2 methyl-CpG-binding protein uncovers a link between DNA methylation and R loops. Thus, our results suggest that a plethora of gene dysfunctions can alter cell physiology via affecting R-loop homeostasis by different mechanisms.

Current treatments for patients with metastatic triple negative breast cancer (TNBC) are generally ineffective. This manuscript shows for the first time that the survival of mice with metastatic TNBC can be markedly increased through dietary manipulation. Our study revealed that the survival of some mice with metastatic TNBC was increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) are manipulated, and the levels of lipids are markedly reduced. The anticancer activity of this non-pharmacological strategy was higher than that of drugs currently used in the treatment of patients with metastatic TNBC. This anticancer strategy also increased the survival of mice with other types of metastatic cancers. Manipulation of AA and lipid levels with artificial diets may be a useful strategy to treat patients with metastatic TNBC and other types of disseminated cancer., Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were also tested in this model. AA manipulation led to modest improvements in mice survival when the levels of lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Some mice fed the artificial diets as monotherapy lived much longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

first_pagesettingsOrder Article Reprints Open AccessArticle Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells by Emilio Guillén-Mancina 1,†,María del Rosario García-Lozano 2,3,†ORCID,Estefanía Burgos-Morón 1ORCID,Sarah Mazzotta 2,4ORCID,Pablo Martínez-Aguado 2,3,5,6,José Manuel Calderón-Montaño 1ORCID,José Manuel Vega-Pérez 2,Miguel López-Lázaro 1ORCID,Fernando Iglesias-Guerra 2,* andMargarita Vega-Holm 2,*ORCID 1 Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 2 Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 3 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, 41013 Seville, Spain 4 Department of Chemistry, University of Milan, 20133 Milan, Italy 5 Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena, 41009 Seville, Spain 6 Departament of Medicine, School of Medicine, University of Seville, 41012 Seville, Spain * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(23), 17041; https://doi.org/10.3390/ijms242317041 Original submission received: 31 January 2023 / Resubmission received: 3 November 2023 / Revised: 21 November 2023 / Accepted: 28 November 2023 / Published: 1 December 2023 (This article belongs to the Special Issue Novel Molecular Pathways in Oncology) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has b

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation.

El Mieloma Múltiple es una neoplasia hematológica muy compleja y de difícil diagnóstico precoz. La incidencia de esta enfermedad aumenta con la edad, diagnosticándose con mayor frecuencia en personas de 65 a 74 años. Aunque las tasas de supervivencias de estos pacientes son elevadas, se trata de una patología incurable. La terapia del mieloma depende de los parámetros específicos de la propia enfermedad y de los factores inherentes al paciente. Normalmente, se realiza terapia de inducción seguida de consolidación con quimioterapia y trasplante autólogo de células madre. Actualmente, existen numerosos fármacos comercializados para el tratamiento del Mieloma Múltiple. Sin embargo, debido a que es una enfermedad caracterizada por recaídas y resistencias a los tratamientos, se siguen realizando estudios de nuevos fármacos. El objetivo principal de este trabajo ha sido realizar una revisión bibliográfica centrada en la farmacoterapia en estudio del mieloma; concretamente, en los nuevos tratamientos en ensayos clínicos de fase III para el Mieloma Múltiple durante los últimos cinco años. Se han realizado búsquedas en diferentes fuentes bibliográficas como webs oficiales de instituciones sanitarias y asociaciones, y bases de datos científicas como PubMed o ClinicalTrials.gov. Se han revisado fármacos pertenecientes a cuatro tipos de grupos farmacoterapéuticos, destacando el anticuerpo monoclonal isatuximab. Este fármaco reconoce antígenos específicos en la superficie de las células plasmáticas malignas e induce su muerte por diferentes mecanismos. Este fármaco fue aprobado en 2021 por la Agencia Española de Medicamentos y Productos Sanitarios, pero continua en estudio para valorar su posible combinación con otros fármacos anticancerosos. Además de este, hay muchos otros fármacos en estudio que auguran resultados prometedores para su uso clínico en Mieloma Múltiple.

Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Lip for delivering anticancer drugs. Nucleolipids have been studied as scaffolding material to prepare Lip, mainly for cancer therapy. Herein, we report for the first time the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) to develop pH/thermo-sensitive nucleolipid-containing stealth Lip stabilized by combination with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, anchored with NH2-PEGylated gold nanoparticles (PEG-AuNPs, 15 nm) for triggering delivery of doxorubicin (Dox). The optimal composition of DPPC, DG-CDP and cholesterol (94:3:3) was established by Langmuir isotherms. Unloaded and Dox-loaded Lip and AuNPs-Lip exhibited nano-scale sizes (415–650 nm), acceptable polydispersity indexes (<0.33), spherical shapes, and negative Z-potential (−23 to −6.6 mV) due to the phosphate groups of DG-CDP, which allowed the anchoring with positively charged AuNPs. High EE% were achieved (>78%) and although efficient control in the Dox release towards different receptor media was observed, the release of Dox from PEG-AuNPs-Lip-Dox was significantly triggered at acidic pH and hyperthermia conditions, demonstrating its responsiveness to both stimuli. Dox-loaded Lip showed high cytotoxic activity against MDA-MB-231 breast cancer cells and SK-OV-3 ovarian cancer cells, suggesting that Dox was released from these nanocarriers over time. Overall, the liposomal formulations showed promising properties as stimuli-responsive nanocarriers for cancer nanomedicine, with prospects for hyperthermia therapy.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.

New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in colon cancer. After observing anticancer activity in vitro, we prepared several artificial diets and evaluated their anticancer activity in two challenging animal models of metastatic colon cancer. These models were established by injecting CT26.WT murine colon cancer cells in the peritoneum (peritoneal dissemination) or in the tail vein (pulmonary metastases) of immunocompetent BALB/cAnNRj mice. Capecitabine, which is a first-line treatment for patients with metastatic colon cancer, was also evaluated in these models. Mice fed diet TC1 (a diet lacking 10 AAs) and diet TC5 (a diet with 6% casein, 5% glutamine, and 2.5% leucine) lived longer than untreated mice in both models; several mice survived the treatment. Diet TC5 was better than several cycles of capecitabine in both cancer models. Cysteine supplementation blocked the activity of diets TC1 and TC5, but cysteine restriction was not sufficient for activity. Our results indicated that artificial diets based on selective AA restriction have therapeutic potential for colon cancer.

El cáncer de endometrio es el décimo cáncer más frecuente a nivel mundial y el segundo más frecuente a nivel ginecológico. Se divide en cuatro estadios en función de la diseminación del tumor, correspondiendo el estadio IV con la etapa de metástasis. Este cáncer presenta una tasa de supervivencia a 5 años del 90% en caso de estar localizado, mientras que en caso de metástasis es tan sólo del 17%. El abordaje terapéutico del cáncer de endometrio localizado consiste en la extirpación del tumor y en caso de ser necesario, se administran radioterapia y/o quimioterapia adyuvantes. En caso de enfermedad metastásica el tratamiento consiste en la administración sistémica de fármacos, que pueden ser quimioterápicos, terapia dirigida o terapia hormonal. La terapia de primera línea para el tratamiento del cáncer de endometrio metastásico consiste en la administración combinada de dos quimioterápicos, Carboplatino y Paclitaxel, obteniéndose una supervivencia libre de progresión de 15 meses. La terapia hormonal también se considera de primera línea cuando la metástasis no es muy agresiva en pacientes con receptores hormonales activos. Los quimioterápicos ocasionan gran número de efectos adversos al atacar a todas las células del cuerpo, por ello se ha introducido la terapia dirigida a biomarcadores donde los fármacos actúan directamente sobre las células cancerosas, evitando así gran número de efectos adversos. Las principales líneas de investigación actuales se centran en inhibidores de puntos de control inmunitarios, en inhibidores de poli-(ADP)-ribosa polimerasa y en la combinación de fármacos ya utilizados. El futuro de estos ensayos es prometedor y se espera conseguir mejores datos de supervivencia por cáncer de endometrio.

Finding cytotoxic drugs with a high selectivity towards cancer cells is crucial to improve the low survival rates of patients diagnosed with metastatic cancers. Since plants are an important source of anticancer drugs, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity on lung cancer cells versus lung normal cells. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC50 = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil, and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective. Extracts from Cascabela thevetia (L.) Lippold (Apocynaceae), Frangula alnus Mill. (Rhamnaceae), Iberis ciliata subsp. contracta (Pers.) Moreno (Brassicaceae), Juniperus macrocarpa Sm (Cupressaceae), and Pancratium maritimum L. (Amaryllidaceae) also showed selective cytotoxicity (selectivity index > 10). Active extracts were also tested against a panel of cancer cell lines from a variety tissues. The plants identified in this work are potential sources of natural compounds with selective toxicity towards cancer cells.

Antecedentes: El asma es una enfermedad inflamatoria crónica que afecta a las vías respiratorias, que cursa con hiperreactividad bronquial y una obstrucción al flujo aéreo, total o parcialmente reversible. El asma afecta a un amplio número de personas y puede catalogarse dentro de una serie de escalones de gravedad, cada uno de los cuáles presentará un tratamiento concreto. Objetivo: El propósito del presente trabajo es la realización de una búsqueda bibliográfica del tratamiento actual del asma bronquial en función de las características del paciente, que permita al farmacéutico comunitario conocer las estrategias de tratamiento para poder realizar un seguimiento y llevar a cabo una actuación que permita al paciente alcanzar el objetivo terapéutico. Metodología: Se realizó una búsqueda en fuentes bibliográficas como, en bases de datos científicas (Pubmed, Medline Plus, PortalFarma, etc.) y las guías actualizadas del asma elaboradas por CADIME y GEMA. Resultados: Los fármacos que son empleados en el tratamiento del asma se engloban en broncodilatadores y antiinflamatorios. Estos fármacos son utilizados con diferentes dispositivos inhaladores que presentan un modo de empleo distinto. En función de cada dispositivo y estrategia de tratamiento, el paciente debe ser instruido. Desde la farmacia comunitaria, se debe realizar un protocolo de actuación distinto a cada tipo de dispensación, y en caso necesario realizar un seguimiento farmacoterapéutico. Conclusiones: El tratamiento del asma implica la utilización de fármacos a demanda y fármacos de mantenimiento, la mayoría usados por vía inhalatoria, empleados mediante distintas presentaciones que incluyen inhaladores presurizados, de vapor suave, de polvo seco y nebulizadores. La falta de manejo, la falsa seguridad por la ausencia de exacerbaciones y la exposición a factores de riesgos conllevan a un mal manejo de la enfermedad., Background: Asthma is a chronic inflammatory disease that affects the airways, with bronchial hyperresponsiveness and a totally or partially reversible airflow obstruction. It affects a large number of people, which can be classified into a series of severity steps, each of which will present a specific treatment. Objective: The purpose of this work is to carry out a bibliographic search of the current treatment of bronchial asthma based on the characteristics of the patient, which allows the community pharmacist to know the treatment strategies to be able to monitor and carry out an action that allow the patient to achieve the therapeutic goal. Methodology: A bibliographic research was carried out using sources, such as scientific databases(Pubmed, Medline Plus, PortalFarma, etc.), and the updated asthma guidelines from CADIME and GEMA. Results: The drugs that are used in the treatment of asthma are included in bronchodilators and anti-inflammatories, these drugs are used with different devices that present a different mode of use. Depending on each device and treatment strategy, the patient must be instructed. From the community pharmacy, a different action protocol must be carried out for each type of dispensing, and in any case a pharmacotherapeutic follow-up must be carried out. Conclusions: Asthma treatment involves the use of drugs on demand and maintenance drugs, most of them used by inhalation, used in different presentations that include pressurized inhalers, mild vapor, dry powder and nebulizers. Lack of management, false safety due to the absence of exacerbations and exposure to risk factors lead to poor management of the disease.

Stimulus-responsive liposomes (L) for triggering drug release to the target site are particularly useful in cancer therapy. This research was focused on the evaluation of the effects of cholesterol levels in the performance of gold nanoparticles (AuNPs)-functionalized L for controlled doxorubicin (D) delivery. Their interfacial and morphological properties, drug release behavior against temperature changes and cytotoxic activity against breast and ovarian cancer cells were studied. Langmuir isotherms were performed to identify the most stable combination of lipid components. Two mole fractions of cholesterol (3.35 mol% and 40 mol%, L1 and L2 series, respectively) were evaluated. Thin-film hydration and transmembrane pH-gradient methods were used for preparing the L and for D loading, respectively. The cationic surface of L allowed the anchoring of negatively charged AuNPs by electrostatic interactions, even inducing a shift in the zeta potential of the L2 series. L exhibited nanometric sizes and spherical shape. The higher the proportion of cholesterol, the higher the drug loading. D was released in a controlled manner by diffusion-controlled mechanisms, and the proportions of cholesterol and temperature of release media influenced its release profiles. D-encapsulated L preserved its antiproliferative activity against cancer cells. The developed liposomal formulations exhibit promising properties for cancer treatment and potential for hyperthermia therapy.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin−CD34+CD38−), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. Significance: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.