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1.
Plants (Basel) ; 10(10)2021 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34685955

RESUMEN

Eranthis longistipitata Regel is an endemic plant of Central Asia. The flavonoid profile of E. longistipitata leaves was studied by mass spectrometry for the first time (natural populations of Kyrgyzstan and Uzbekistan, in 70% aqueous-ethanol extracts by liquid chromatography coupled with high-resolution mass spectrometry). Mass spectrometry revealed 18 flavonoid compounds. Flavonols featured the highest diversity, and 10 such substances were identified: 2 free aglycones (quercetin and kaempferol), 6 quercetin glycosides (peltatoside, hyperoside, reynoutrin, quercetin 3-sambubioside, rutin, and isoquercitrin), and 2 kaempferol glycosides (juglalin and trifolin). Two flavans (cianidanol and auriculoside), two hydroxyflavanones (6-methoxytaxifolin and aromadendrin), and one C-glycoside flavone-carlinoside-were identified. Dihydroxychalcones aspalathin, phloridzin, and phloretin were found too. Levels of rutin, quercetin, kaempferol, and hyperoside were confirmed by means of standards and high-performance liquid chromatography. Rutin concentration was the highest among all other identified flavonoid compounds: in the leaf samples from Kyrgyzstan, it ranged from 2.46 to 3.20 mg/g, and in those from Uzbekistan, from 1.50 to 3.01 mg/g. The diversity of flavonoid compounds in E. longistipitata leaves is probably due to external ecological and geographic factors and adaptive mechanisms.

2.
Front Immunol ; 10: 2693, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31849934

RESUMEN

Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 µg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 µM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Piperazinas/uso terapéutico , Polímeros/uso terapéutico , Adenocarcinoma/inmunología , Adulto , Anciano , Neoplasias de la Mama/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Quimioterapia Adyuvante/métodos , Células Dendríticas/inmunología , Femenino , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología
3.
Cells ; 8(6)2019 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-31234438

RESUMEN

Disseminated tumor cells (DTCs) are studied as a prognostic factor in many non-hematopoietic tumors. Melanoma is one of the most aggressive tumors. Forty percent of melanoma patients develop distant metastases at five or more years after curative surgery, and frequent manifestations of melanoma without an identified primary lesion may reflect the tendency of melanoma cells to spread from indolent sites such as bone marrow (BM). The purpose of this work was to evaluate the possibility of detecting melanoma DTCs in BM based on the expression of a cytoplasmatic premelanocytic glycoprotein HMB-45 using flow cytometry, to estimate the influence of DTCs' persistence in BM on hematopoiesis, to identify the frequency of BM involvement in patients with melanoma, and to analyze DTC subset composition in melanoma. DTCs are found in 57.4% of skin melanoma cases and in as many as 28.6% of stage I cases, which confirms the aggressive course even of localized disease. Significant differences in the groups with the presence of disseminated tumor cells (DTCs+) and the lack thereof (DTC-) are noted for blast cells, the total content of granulocyte cells, and oxyphilic normoblasts of erythroid raw cells.


Asunto(s)
Médula Ósea/patología , Citometría de Flujo/métodos , Melanoma/patología , Antígeno AC133/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Adulto Joven
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