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The present study characterized a genetically and phenotypically diverse collection of 27 purple and two non-purple (one orange and one yellow) carrot accessions for concentration of root anthocyanins, phenolics, and carotenoids, and antioxidant capacity estimated by four different methods (ORAC, DPPH, ABTS, FRAP), in a partially replicated experimental design comprising data from two growing seasons (2018 and 2019). Broad and significant (p < 0.0001) variation was found among the accessions for all the traits. Acylated anthocyanins (AA) predominated over non-acylated anthocyanins (NAA) in all the accessions and years analyzed, with AA accounting for 55.5-100% of the total anthocyanin content (TAC). Anthocyanins acylated with ferulic acid and coumaric acid were the most abundant carrot anthocyanins. In general, black or solid purple carrots had the greatest TAC and total phenolic content (TPC), and the strongest antioxidant capacities, measured by all methods. Antioxidant capacity, estimated by all methods, was significantly, positively, and moderately-to-strongly correlated with the content of all individual anthocyanins pigments, TAC, and TPC, in both years (r = 0.59-0.90, p < 0.0001), but not with the carotenoid pigments lutein and ß-carotene; suggesting that anthocyanins and other phenolics, but not carotenoids, are major contributors of the antioxidant capacity in purple carrots. We identified accessions with high concentration of chemically stable AA, with potential value for the production of food dyes, and accessions with relatively high content of bioavailable NAA that can be selected for increased nutraceutical value (e.g., for fresh consumption).
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Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inherent to melanoma and how this supports the use of viral oncolysis and immunotherapies when used as monotherapies or in combination.
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ABSTRACT Leishmaniasis is a group of parasitic zoonotic diseases caused by intracellular protozoans belonging to the genusLeishmania. Little is known about the effects that this parasitosis may have on the reproductive parameters and pregnancy of infected humans and pets. This study aimed to evaluate the influence of chronic cutaneous leishmaniasis caused byLeishmania (Leishmania) amazonensison reproductive and fetal parameters using a female murine model. A control group of female BALB/c mice and a group infected withL. (L.) amazonensiswere mated with healthy males. Clinical parameters were monitored during the pre-mating and gestational periods. Female mice were euthanized on day 19 of gestation, when the fetuses were weighed and their length measured and embryonic resorptions and fetal death were recorded. We observed five fetal deaths and three embryonic resorptions in the infected group. Furthermore, there was a decrease in fertility in the infected group (26.32%). The weight of the offspring from infected mothers was lower than that in the control group (1.019±0.035g and 1.163±0.032g,p<0.01). Fetal length was reduced in the infected group (3.71±0.05cm in the control group and 3.40±0.06cm in the infected groupp<0.001). This study shows that cutaneous leishmaniasis caused byL. (L.) amazonensisimpairs reproductive and fetal parameters in mice.
RESUMEN La leishmaniasis comprende un grupo de enfermedades zoonóticas parasitarias causadas por protozoos intracelulares pertenecientes al géneroLeishmania. Poco se conoce sobre los efectos que esta parasitosis puede tener sobre los parámetros reproductivos y la gestación en humanos y en otras especies infectadas. El objetivo de este estudio fue determinar la influencia de la leishmaniasis cutánea crónica, causada porLeishmania (Leishmania) amazonensis, en parámetros reproductivos y fetales. Se apareó un grupo control y un grupo infectado de ratones hembra BALB/c (previamente inoculado conL. (L.) amazonensis) con machos sanos. Se analizaron parámetros clínicos durante los períodos pregestacional y gestacional. Las hembras fueron eutanasiadas en el día 19 de gestación, momento en el cual se pesaron y midieron los fetos y se registraron las reabsorciones embrionarias y las muertes fetales. Se observaron 5 muertes fetales y 3 reabsorciones embrionarias en el grupo infectado. Además, hubo una disminución en la fertilidad de este último grupo (26,32%). Por otra parte, el peso de la descendencia de madres infectadas fue menor que el del grupo control (1,019±0,035g y 1,163±0,032g, respectivamente,p<0,01). Por último, la longitud fetal se redujo en el grupo infectado (3,71±0,05cm en el grupo control y 3,40±0,06cm en el grupo infectado,p<0,001). Este estudio muestra que la leishmaniasis cutánea causada porL. (L.) amazonensisafecta los parámetros reproductivos y fetales en ratones.
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Animales , Femenino , Masculino , Ratones , Embarazo , Leishmaniasis Cutánea , Leishmania , Feto , Ratones Endogámicos BALB CRESUMEN
Reversible electropermeabilization (RE) is an ultrastructural phenomenon that transiently increases the permeability of the cell membrane upon application of electrical pulses. The technique was described in 1972 by Neumann and Rosenheck and is currently used in a variety of applications, from medicine to food processing. In oncology, RE is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. This review summarizes the physical changes of the membrane, the particularities of bleomycin, and the immunological aspects involved in electrochemotherapy and gene electrotransfer, two important EP-based cancer therapies in human and veterinary oncology.
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This paper is a contribution to the current knowledge of taxonomy, ecology and distribution of South American Cortinarius (Pers.) Gray. Cortinarius is among the most widely distributed and species-rich basidiomycete genera occurring with South American Nothofagaceae and species are found in many distinct habitats, including shrublands and forests. Due to their ectomycorrhizal role, Cortinarius species are critical for nutrient cycling in forests, especially at higher latitudes. Some species have also been reported as edible fungi with high nutritional quality. Our aim is to unravel the taxonomy of selected Cortinarius belonging to phlegmacioid and myxotelamonioid species based on morphological and molecular data. After widely sampling Cortinarius specimens in Patagonian Nothofagaceae forests and comparing them to reference collections (including holotypes), we propose five new species of Cortinarius in this work. Phylogenetic analyses of concatenated rDNA ITS-LSU and RPB1 sequences failed to place these new species into known Cortinarius sections or lineages. These findings highlight our knowledge gaps regarding the fungal diversity of South American Nothofagaceae forests. Due to the high diversity of endemic Patagonian taxa, it is clear that the South American Cortinarius diversity needs to be discovered and described in order to understand the evolutionary history of Cortinarius on a global scale.
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Leishmaniasis is a group of parasitic zoonotic diseases caused by intracellular protozoans belonging to the genus Leishmania. Little is known about the effects that this parasitosis may have on the reproductive parameters and pregnancy of infected humans and pets. This study aimed to evaluate the influence of chronic cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis on reproductive and fetal parameters using a female murine model. A control group of female BALB/c mice and a group infected with L. (L.) amazonensis were mated with healthy males. Clinical parameters were monitored during the pre-mating and gestational periods. Female mice were euthanized on day 19 of gestation, when the fetuses were weighed and their length measured and embryonic resorptions and fetal death were recorded. We observed five fetal deaths and three embryonic resorptions in the infected group. Furthermore, there was a decrease in fertility in the infected group (26.32%). The weight of the offspring from infected mothers was lower than that in the control group (1.019±0.035g and 1.163±0.032g, p<0.01). Fetal length was reduced in the infected group (3.71±0.05cm in the control group and 3.40±0.06cm in the infected group p<0.001). This study shows that cutaneous leishmaniasis caused by L. (L.) amazonensis impairs reproductive and fetal parameters in mice.
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Leishmania , Leishmaniasis Cutánea , Animales , Femenino , Feto , Masculino , Ratones , Ratones Endogámicos BALB C , EmbarazoRESUMEN
Immune evasion is an important cancer hallmark and the understanding of its mechanisms has generated successful therapeutic approaches. Induction of immunogenic cell death (ICD) is expected to attract immune cell populations that promote innate and adaptive immune responses. Here, we present a critical advance for our adenovirus-mediated gene therapy approach, where the combined p14ARF and human interferon-ß (IFNß) gene transfer to human melanoma cells led to oncolysis, ICD and subsequent activation of immune cells. Our results indicate that IFNß alone or in combination with p14ARF was able to induce massive cell death in the human melanoma cell line SK-MEL-147, though caspase 3/7 activation was not essential. In situ gene therapy of s.c. SK-MEL-147 tumors in Nod-Scid mice revealed inhibition of tumor growth and increased survival in response to IFNß alone or in combination with p14ARF. Emission of critical markers of ICD (exposition of calreticulin, secretion of ATP and IFNß) was stronger when cells were treated with combined p14ARF and IFNß gene transfer. Co-culture of previously transduced SK-MEL-147 cells with monocyte-derived dendritic cells (Mo-DCs) derived from healthy donors resulted in increased levels of activation markers HLA-DR, CD80, and CD86. Activated Mo-DCs were able to prime autologous and allogeneic T cells, resulting in increased secretion of IFNγ, TNF-α, and IL-10. Preliminary data showed that T cells primed by Mo-DCs activated with p14ARF+IFNß-transduced SK-MEL-147 cells were able to induce the loss of viability of fresh non-transduced SK-MEL-147 cells, suggesting the induction of a specific cytotoxic population that recognized and killed SK-MEL-147 cells. Collectively, our results indicate that p14ARF and IFNß delivered by our adenoviral system induced oncolysis in human melanoma cells accompanied by adaptive immune response activation and regulation.
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Adenoviridae/fisiología , Inmunoterapia/métodos , Interferón beta/genética , Melanoma/terapia , Linfocitos T/inmunología , Proteína p14ARF Supresora de Tumor/genética , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Terapia Genética , Humanos , Activación de Linfocitos , Melanoma/genética , Ratones , Ratones SCID , Viroterapia Oncolítica , Carga Tumoral , Escape del TumorRESUMEN
BACKGROUND Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.
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Leishmania , Vacunas contra la Leishmaniasis , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/prevención & control , Vacunas Antiprotozoos/inmunología , Receptor Toll-Like 3/inmunología , Animales , Antígenos de Protozoos/inmunología , Humanos , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.
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Humanos , Animales , Ratones , Vacunas Antiprotozoos/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/prevención & control , Receptor Toll-Like 3/inmunología , Vacunas contra la Leishmaniasis , Leishmania , Ratones Endogámicos BALB C , Antígenos de Protozoos/inmunologíaRESUMEN
Breast cancer (BC) remains the leading cause of cancer-related deaths among women, and the chances to develop it are duplicated by obesity. Still, the impact of obesity during BC progression remains less understood. We investigated the role of obesity in tumor progression using the murine model of 4T1 mammary carcinoma in BALB/c female mice, previously high-fat-diet (HFD) fed. HFD induced obesity, metabolic impairment, and high serum and fat leptin levels. After injection of 4T1-cells, HFD-mice accelerated tumor progression and metastasis. 4T1-cells found within HFD-mice metastatic niches presented higher clonogenic potential. 4T1-cells treated in vitro with fat-conditioned medium derived from HFD-mice, increased migration capacity through CXCL12 and CCL25 gradients. In HFD-mice, the infiltration and activation of immune cells into tumor-sentinel lymph nodes was overall reduced, except for activated CD4+ T cells expressing low CD25 levels. Within the bone marrow, the levels of haematopoiesis-related IL-6 and TNF-α decreased after 4T1-cells injection in HFD-mice whereas increased in the controls, suggesting that upregulation of both cytokines, regardless of the tumor, is disrupted by obesity. Finally, the expression of genes for leptin, CXCR4, and CCR9 (receptors of CXCL12 and CCL25, respectively) was negatively correlated with the infiltration of CD8 T cells in human triple-negative BC tumors from obese patients compared to non-obese. Together, our data present early evidence of systemic networks triggered by obesity that promote BC progression to the metastatic niches. Targeting these pathways might be useful to prevent the rapid BC progression observed among obese patients.
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Of the three Trichinella species described in South America, T. spiralis, T. pseudospiralis and T. patagoniensis, only the former has been implicated in human infections from consumption of pork-derived products. During a presumed trichinellosis outbreak in 2012 in Mendoza, Argentina, we evaluated the serological responses of three patients who had eaten the incriminated food and had signs and symptoms compatible with trichinellosis, using ELISA. We also analyzed potentially contaminated pork sausage by artificial digestion technique and recovered Trichinella muscle larvae, which were identified to the species level using a PCR multiplex assay and by sequencing a region of the mitochondrial gene coding cytochrome oxidase subunit I. No antibodies were detected in the sera of the patients, probably because the samples were collected during the immunological window period. According to molecular identification, all larvae from the sausage corresponded to T. britovi. Trichinella britovi is reported here for the first time in the American Continent, and represents the only cold-tolerant member of the genus in the Neotropics. This species was most likely introduced from Europe to South America during Spanish colonization through pigs, wild boars and/or rats.
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Brotes de Enfermedades , Enfermedades Transmitidas por los Alimentos/parasitología , Productos de la Carne/parasitología , Trichinella/aislamiento & purificación , Triquinelosis/etiología , Adulto , Animales , Anticuerpos Antihelmínticos/sangre , Argentina/epidemiología , Complejo IV de Transporte de Electrones/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Larva/genética , Masculino , Reacción en Cadena de la Polimerasa , Porcinos , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/transmisión , Trichinella/genética , Triquinelosis/epidemiologíaRESUMEN
Cortinarius magellanicus Speg. is an edible, ectomycorrhizal fungus, widely distributed in Argentina, Chile and New Zealand. However, earlier studies already indicated that the epithet 'magellanicus' might have been applied in a wide sense, thus circumscribing several species. A neotype was designated by Moser and Horak (1975) due Spegazzini's type was lost. Argentinian Nothofagaceae forests' samples, from autumn of 2017, morphologically recognized as C. magellanicus were used for a phylogenetic analysis, including sequences from type material and closely related species. Our results showed that C. magellanicus represents a complex of species, with at least three phylogenetic lineages, each with strong regionalism and distinct host associations. Cortinarius magellanicus s. str. is restricted to Patagonia of Argentina and Chile. The misidentified reports from New Zealand and Australia represent distinct and different lineages. In the present contribution, the re-description of C. magellanicus is based on neotype material and two new species are proposed. Cortinarius vitreopileatus var. similissimus is described as variety from New Zealand resembling C. magellanicus, however without close phylogenetic relationship to it. The taxonomic delimitation for C. magellanicus species complex is of high relevance due to the abundance of these fungi and their ectomycorrhizal role in Nothofagaceae forests in Gondwanian region.
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Cortinarius/aislamiento & purificación , Magnoliopsida/microbiología , Micorrizas/aislamiento & purificación , Argentina , Australia , Chile , Cortinarius/clasificación , Cortinarius/genética , Cortinarius/crecimiento & desarrollo , Ecosistema , Bosques , Micorrizas/clasificación , Micorrizas/genética , Micorrizas/crecimiento & desarrollo , Nueva Zelanda , Filogenia , Esporas Fúngicas/clasificación , Esporas Fúngicas/genética , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/aislamiento & purificaciónRESUMEN
Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
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Factor Estimulante de Colonias de Granulocitos/sangre , Evasión Inmune , Neutrófilos/inmunología , Papillomaviridae/inmunología , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Células Dendríticas/inmunología , Femenino , Humanos , Macrófagos/inmunología , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Linfocitos T/inmunología , Adulto JovenRESUMEN
With the enormous and growing interest in the clinical application of immunotherapy, we are currently facing the need to accurately monitor the immune function of cancer patients. Here, we describe changes in the immune status of a patient with metastatic type-2-papillary renal cell carcinoma, before and after surgery and subsequent immunotherapy with a dendritic cell-tumor cell hybrid vaccine. Through the accurate assessment of monocyte-derived dendritic cells (Mo-DCs) function, we show that Mo-DCs were freed from tumor-induced maturation blockage by tumor resection surgery, while Mo-DCs-tumor induced suppression and anergy were only interrupted by the vaccination treatment. Our data suggest that the evaluation of Mo-DCs' function may provide a powerful and precise tool to monitor immune restoration in cancer patients.
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Vacunas contra el Cáncer/inmunología , Carcinoma de Células Renales/terapia , Células Dendríticas/fisiología , Inmunoterapia/métodos , Neoplasias Renales/terapia , Monitorización Inmunológica , Linfocitos T Reguladores/inmunología , Adulto , Antígenos de Neoplasias/inmunología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Citocinas/metabolismo , Células Dendríticas/trasplante , Humanos , Terapia de Inmunosupresión , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Masculino , Escape del Tumor/efectos de los fármacos , VacunaciónRESUMEN
American tegumentary leishmaniasis is the generic name for a variety of cutaneous and mucocutaneous presentations of parasitosis caused by several species of the genus Leishmania. This is a widespread infection in the American continent, from the South of the United States to the North of Argentina. We herein describe the management of a patient with American tegumentary leishmaniasis in Mendoza, Argentina, a nonendemic area of South America, whose diagnosis and treatment were significantly delayed, because the patient did not report a recent history of travel to any known endemic areas. This case stresses the need for training health-care professionals in the diagnosis and treatment of not only endemic parasitosis within their work zones but also nonendemic parasitosis.
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Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitología , Argentina , Femenino , Humanos , Leishmaniasis Cutánea/terapia , Viaje , Adulto JovenRESUMEN
PURPOSE: The chromophobe renal cell carcinoma (ChRCC), though associated with a hereditary cancer syndrome, has a good prognosis after tumor removal. The lack of recurrence could be related to the absence of immune system compromise in patients or to an effective functional recovery of immune functions after tumor removal. Thus, we evaluated monocyte-derived dendritic cells (Mo-DCs) in a 34-year-old male who had a ChRCC, before and after tumor removal. METHODS: CD14(+) monocytes from the patient's peripheral blood, 1 week before and 3 months after partial nephrectomy, were differentiated in vitro into immature and mature Mo-DCs. These were harvested, analyzed by flow cytometry and used as stimulators of allogeneic T cells. Supernatants from cultures were collected for cytokine analysis. RESULTS: Tumor removal was associated with decreased expression of PD-L1, but also, surprisingly, of CD205, HLA-DR, CD80 and CD86 by Mo-DCs. Also, Mo-DC's ability to stimulate T cell proliferation increased, along with IL-2Rα expression and IFN-γ production. Simultaneously, the patients' Mo-DCs ability to induce Foxp3(+) T cells decreased after surgery. One-year postoperative follow-up shows no tumor recurrence. CONCLUSION: The presence of a ChRCC affected Mo-DCs generated in vitro, which recovered their function after tumor removal. This indicates that the favorable outcome observed after ChRCC resection may be due to the restoration of immunocompetence. Furthermore, since functional alterations described for DCs within tumors may be also found in Mo-DCs, their accurate functional analysis-not restricted to the determination of their surface immunophenotype-may provide an indirect "window" to the tumor microenvironment.
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Carcinoma de Células Renales/inmunología , Células Dendríticas/inmunología , Neoplasias Renales/inmunología , Monocitos/inmunología , Adulto , Antígenos de Superficie/metabolismo , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/cirugía , Diferenciación Celular , Citocinas/metabolismo , Células Dendríticas/citología , Células Dendríticas/metabolismo , Humanos , Inmunofenotipificación , Neoplasias Renales/diagnóstico , Neoplasias Renales/metabolismo , Neoplasias Renales/cirugía , Masculino , Monocitos/citología , Monocitos/metabolismo , Fenotipo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.
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Antineoplásicos/administración & dosificación , Benzoxazoles/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Niacinamida/administración & dosificación , SorafenibRESUMEN
Eleven bacterial strains were isolated at different soil depths from roots and rhizosphere of grapevines from a commercial vineyard. By 16S rRNA gene sequencing 10 different genera and 8 possible at species level were identified. From them, Bacillus licheniformis Rt4M10 and Pseudomonas fluorescens Rt6M10 were selected according to their characteristics as plant growth promoting rhizobacteria (PGPR). Both produced abscisic acid (ABA), indole-3-acetic acid (IAA) and the gibberellins A1 and A3 in chemically-defined medium. They also colonized roots of in vitro grown Vitis vinifera cv. Malbec plants. As result of bacterization ABA levels in 45 days-old in vitro plants were increased 76-fold by B. licheniformis and 40-fold by P. fluorescens as compared to controls. Both bacteria diminished plant water loss rate in correlation with increments of ABA. Twenty and 30 days post bacterization the plants incremented terpenes. The monoterpenes α-pinene, terpinolene, 4-carene, limonene, eucalyptol and lilac aldehyde A, and the sesquiterpenes α-bergamotene, α-farnesene, nerolidol and farnesol were assessed by gas chromatography-electron impact mass spectrometry analysis. α-Pinene and nerolidol were the most abundant (µg per g of tissue in plants bacterized with P. fluorescens). Only α-pinene, eucalyptol and farnesol were identified at low concentration in non-bacterized plants treated with ABA, while no terpenes were detected in controls. The results obtained along with others from literature suggest that B. licheniformis and P. fluorescens act as stress alleviators by inducing ABA synthesis so diminishing water losses. These bacteria also elicit synthesis of compounds of plant defense via an ABA independent mechanism.
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Ácido Abscísico/metabolismo , Bacterias/aislamiento & purificación , Raíces de Plantas/microbiología , Transpiración de Plantas , Rizosfera , Terpenos/metabolismo , Vitis/microbiología , Ácido Abscísico/farmacología , Bacterias/crecimiento & desarrollo , Recuento de Colonia Microbiana , Cromatografía de Gases y Espectrometría de Masas , Concentración de Iones de Hidrógeno , Ácidos Indolacéticos/metabolismo , Filogenia , Transpiración de Plantas/efectos de los fármacos , ARN Ribosómico 16S/genética , Terpenos/química , Técnicas de Cultivo de Tejidos , Vitis/inmunología , Vitis/fisiologíaRESUMEN
La difilobotriosis es una parasitosis intestinal causada por la infección de cestodos del genero Diphyllobothrium. En la Argentina, la Patagonia Andina es considerada una zona endémica para esta parasitosis. La infección por Diphyllobothrium latum no ha sido previamente notificada en la provincia de Mendoza; en este trabajo comunicamos un caso de esta parasitosis que fue confirmada por el análisis de las características morfológicas de los huevos eliminados con la materia fecal de un paciente infectado. Se destaca la necesidad de información y capacitación de los profesionales de la salud en el diagnóstico y tratamiento de parasitosis no endémicas.(AU)
Diphyllobothriosis is an intestinal parasitosis caused by cestodes infection of the genus Diphyllobothrium. In Argentina, the Andean Patagonia is considered an endemic area for this parasitosis. Diphyllobothrium latum infection has not been previously reported in the province of Mendoza, Argentina. We are now reporting then the first case. Diphyllobothriosis was confirmed by examination of morphologic characteristics of the eggs eliminated in the patients feces. These results suggest the requirement of a more specific training of health workers in the diagnosis and treatment of non endemic parasitosis. We want to emphasize the need of health workers education on diagnosis and treatment of endemic and non-endemic parasitosis.(AU)
Asunto(s)
Animales , Humanos , Masculino , Adulto Joven , Difilobotriosis/diagnóstico , Diphyllobothrium/aislamiento & purificación , Parasitología de Alimentos , Oncorhynchus kisutch/parasitología , Argentina/epidemiología , Recuento de Huevos de ParásitosRESUMEN
La difilobotriosis es una parasitosis intestinal causada por la infección de cestodos del genero Diphyllobothrium. En la Argentina, la Patagonia Andina es considerada una zona endémica para esta parasitosis. La infección por Diphyllobothrium latum no ha sido previamente notificada en la provincia de Mendoza; en este trabajo comunicamos un caso de esta parasitosis que fue confirmada por el análisis de las características morfológicas de los huevos eliminados con la materia fecal de un paciente infectado. Se destaca la necesidad de información y capacitación de los profesionales de la salud en el diagnóstico y tratamiento de parasitosis no endémicas.(AU)
Diphyllobothriosis is an intestinal parasitosis caused by cestodes infection of the genus Diphyllobothrium. In Argentina, the Andean Patagonia is considered an endemic area for this parasitosis. Diphyllobothrium latum infection has not been previously reported in the province of Mendoza, Argentina. We are now reporting then the first case. Diphyllobothriosis was confirmed by examination of morphologic characteristics of the eggs eliminated in the patients feces. These results suggest the requirement of a more specific training of health workers in the diagnosis and treatment of non endemic parasitosis. We want to emphasize the need of health workers education on diagnosis and treatment of endemic and non-endemic parasitosis.(AU)