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1.
Ann Hematol ; 94(8): 1319-26, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25869029

RESUMO

In the present analysis, we evaluated whether in elderly acute myeloid leukemia (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow cytometry may have a role in guiding choice of postremission strategies. We analyzed 149 young and 61 elderly adults who achieved morphological CR after induction course of EORTC/GIMEMA protocols. Elderly patients reached a postconsolidation MRD negative status less frequently than younger ones (11 vs 28 %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31 %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative elderly patients was twofold higher than that of younger MRD negative ones (42 vs 24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD negative CR have duration of DFS and rate of CIR significantly better than those who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly suggests that MRD negativity might have different therapeutic implications in this population than in the younger counterpart.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Indução de Remissão , Prevenção Secundária/métodos , Adulto Jovem
2.
Perfusion ; 28(4): 298-305, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23411504

RESUMO

Hemostasis is impaired during CABG and coagulation abnormalities often result in clinically relevant organ dysfunctions, eventually increasing morbidity and mortality rates. Fifteen consecutive patients with coronary artery disease submitted to conventional extracorporeal circulation (cECC) have been compared with 15 matched patients, using mini-ECC (MECC). Postoperative lung function was evaluated according to gas exchange, intubation time and lung injury score. In the MECC group, thrombin-antithrombin complex levels (TaTc), prothrombin fragments (PF1+2) formation and thromboelastography (TEG) clotting times were lower compared to the cECC group (p=0.002 and p<0.001, respectively) whereas postoperative blood loss was higher in the cECC group (p=0.030) and more patients required blood transfusion (p=0.020). In the MECC group, postoperative gas exchange values were better, intubation time shorter and lung injury score lower (p<0.001 for all comparisons). Our study suggests that MECC induces less coagulation disorders, leading to lower postoperative blood loss and better postoperative lung function. This approach may be advantageous in high-risk patients.


Assuntos
Coagulação Sanguínea , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/instrumentação , Circulação Extracorpórea/efeitos adversos , Circulação Extracorpórea/instrumentação , Pulmão/fisiopatologia , Idoso , Feminino , Humanos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Tromboelastografia
3.
G Ital Dermatol Venereol ; 148(5): 471-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24005139

RESUMO

AIM: This study assesses the efficacy of a new non steroid anti-inflammatory product in comparison to Hydrocortisone Butyrate 0.1% Cream in healing eczematous dermatitis. METHODS: A bilateral controlled randomized pilot study was conducted in Italian adults affected by eczema with at least two symmetric lesions at baseline, respectively assigned to a non steroid cream or Hydrocortisone. The severity of lesions was judged through the Global Clinical Score (GCS) and the recovery was defined as a GSC equal to 0. The study investigated: 1) the differences in GCS between four points in time during therapy (baseline, four, eight, twelve weeks), according to medication received; 2) treatment efficacy. RESULTS: The study showed that time, treatment and interaction between treatment and time were associated with GCS; moreover, lesions treated with Hydrocortisone went better on the whole but the post-hoc analysis showed a significant clinical improving at each point in time only for the non steroid cream. At the end of the study, in the intention to treat analysis, lesions recovered in 76.1% and 40.3% patients treated with Hydrocortisone and with the non steroid cream respectively; in the per protocol population, recovery was achieved in 91.7% and 58.3% of cases. CONCLUSION: According to the results, the non steroid cream has been demonstrated effective in reducing the severity of eczema and may be used with continuing success in the long term treatment of the disease.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Eczema/tratamento farmacológico , Ácido Glicirrízico/análogos & derivados , Administração Cutânea , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Emolientes/administração & dosagem , Emolientes/uso terapêutico , Feminino , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/uso terapêutico , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pomadas , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
4.
Leukemia ; 37(12): 2383-2394, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37803061

RESUMO

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.


Assuntos
Leucemia Mieloide Aguda , Metformina , Humanos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , RNA Interferente Pequeno , Invasividade Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica
5.
Leuk Res ; 127: 107040, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36801702

RESUMO

We compared the efficacy of azacitidine (AZA) and decitabine (DEC) in elderly patients with untreated AML, diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS) and disease free survival (DFS). The AZA and DEC groups included 139 and 186 patients, respectively. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 136 patient pairs. In the AZA and DEC cohort, median age was 75 years in both, (IQR, 71-78 and 71-77), median WBCc at treatment onset 2.5 × 109/L (IQR, 1.6-5.8) and 2.9 × 109/L (IQR, 1.5-8.1), median bone marrow (BM) blast count 30% (IQR, 24-41%) and 49% (IQR, 30-67%), 59 (43%) and 63 (46%) patients had a secondary AML, respectively. Karyotype was evaluable in 115 and 120 patients: 80 (59%) and 87 (64%) had intermediate-risk, 35 (26%) and 33 (24%) an adverse risk karyotype, respectively. Median number of cycles delivered was 6 (IQR, 3.0-11.0) and 4 (IQR, 2.0-9.0), CR rate was 24% vs 29%, median OS and 2-year OS rates 11.3 (95% CI 9.5-13.8) vs 12.0 (95% CI 7.1-16.5) months and 20% vs 24%, respectively. No differences in CR and OS were found within the following subgroup: intermediate- and adverse-risk cytogenetic, frequency of WBCc at treatment ≥ 5 × 10^9 L and < 5 × 10^9/L, de novo and secondary AML, BM blast count < and ≥ 30%. Median DFS for AZA and DEC treated patients was 9.2 vs 12 months, respectively. Our analysis indicates similar outcomes with AZA compared to DEC.


Assuntos
Azacitidina , Leucemia Mieloide Aguda , Humanos , Idoso , Azacitidina/uso terapêutico , Decitabina/uso terapêutico , Resultado do Tratamento , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
Ann Oncol ; 23(6): 1499-502, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22039089

RESUMO

BACKGROUND: The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS: Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS: An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION: Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Plasmocitária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos/administração & dosagem , Bortezomib , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Plasmocitária/mortalidade , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Pirazinas/administração & dosagem , Estudos Retrospectivos , Talidomida/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem
7.
Ann Oncol ; 22(7): 1628-1635, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21252060

RESUMO

BACKGROUND: Epidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in pPCL. PATIENTS AND METHODS: A multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30). RESULTS: Sixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT. CONCLUSIONS: pPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Plasmocitária/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Ácidos Borônicos/administração & dosagem , Bortezomib , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Talidomida/administração & dosagem , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
8.
Semin Hematol ; 56(2): 125-130, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926088

RESUMO

Despite the increasing knowledge of the genomic landscape of acute myeloid leukemia (AML), prediction merely based on genetics fails to anticipate outcome, presumably due to the heterogeneous composition of the leukemic clone determining complex interactions between different genetic abnormalities. Therefore, the introduction of a post-treatment biomarker exploring the quality of response to therapy such as assessment of measurable (previously minimal) residual disease (MRD) may lead to refinements of the prognostic assessment in AML. In this view, the European LeukemiaNet has recently endorsed the achievement of a MRD negative morphologic complete remission as a purpose the treatment. Techniques like multiparametric flow cytometry and reverse transcriptase-quantitative polymerase chain reaction have reached a level of sensitivity and specificity that make them ready for introduction in clinical practice. In the present review, we will give an update on the efforts in harmonization and/or standardization of MRD assessment in AML, focusing on the newest acquisitions in the clinical applications of MRD, and considering issues like relationship of MRD with leukemic stem cells or MRD assessment in peripheral blood.


Assuntos
Leucemia Mieloide Aguda/complicações , Neoplasia Residual/etiologia , Humanos , Neoplasia Residual/patologia , Prognóstico
9.
Leukemia ; 20(10): 1783-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16838027

RESUMO

UNLABELLED: We assessed by multiparametric flow cytometry the levels of minimal residual disease (MRD) in 100 adult patients with acute myelogenous leukemia (AML) achieving complete remission after intensive chemotherapy. The aim of the study was to determine the optimal threshold, in terms of residual leukemic cells, and the time point of choice, that is, post-induction (post-Ind) or post-consolidation (post-Cons), able to better predict outcome. By applying the maximally selected log-rank statistics, the threshold discriminating MRD- from MRD+ cases was set at 3.5 x 10(-4) residual leukemic cells, a level that allowed the identification of distinct subgroups of patients, both at post-Ind and post-Cons time points. Post-Cons MRD- patients had a superior outcome in terms of relapse rate, overall survival (OS) and relapse-free survival (RFS) (P<0.001, for all comparisons), regardless of the MRD status after induction. In particular, patients entering MRD negativity only after consolidation showed the same outcome as those achieving early negativity after induction. Multivariate analysis, including karyotype, age, MDR1 phenotype, post-Ind and post-Cons MRD levels, indicated that the post-Cons MRD status independently affected relapse rate, OS and RFS (P<0.001, for all comparisons). IN CONCLUSION: (1) the threshold of 3.5 x 10(-4) is valid in discriminating risk categories in adult AML and (2) post-Cons MRD assessment is critical to predict disease outcome.


Assuntos
Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Cinética , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Análise de Sobrevida
10.
Oral Implantol (Rome) ; 10(4): 406-411, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29682258

RESUMO

BACKGROUND: The purpose of the study is to evaluate the effectiveness of Low-Level Laser Therapy in reducing joint and muscle pain in patients with acute and chronic temporomandibular dysfunction. MATERIALS AND METHODS: The study was conducted on a sample of 180 patients. The sample was divided into two groups according to the time of onset of the disease: acute TMD (<6 months) and chronic TMD (> 6 months). The treatment for all patients provided for the irradiation with Diode Laser Wiser Doctor Smile with tip plane wave at wavelength of 830 nm, continuous beam to 40nW diameter and radius of 6 mm. The irradiated areas were the joint area, temporal, masseter and pterygoid. The irradiation time for each zone was 60s.The protocol adopted consisted of two weekly treatment for six weeks. Pain assessment was performed using the Visual Analog Scale (VAS), in which different scores (s) depending accused of pain by the patient: s0 no pain, s1-3 mild pain, s4-6 moderate pain, s7-9 severe pain and s10 excessive pain. The pain monitoring was performed before treatment, after 15 days and after one month. RESULTS: The sample included 80 patients with acute TMD and 100 with chronic TMD. The sample belonging to acute TMD group before treatment, was distributed as follows: 0% in s0; 12,5% in s1-3; 31.3% in s4-6; 53.6% in s7-9 and 2.5% in s10. After 15 days the distribution was was as follows: 6.25% in s0; 47.5% in s1-3; 20% in s4-6; 26.3% in s7-9 and 0% in s10. After 30 days the sample was well distributed: 35% in s0; 45% in 1-3; 10% in s4-6; 10% in s7-9 and 0% in s10. The sample belonging to the chronic TMD group, at time zero, was as follows: 0% at s0; 48% in S1-3; 35% in s4-6; 15% in s7-9 and 2% in s10. After 15 days the distribution was: 29% in s0; 28% in S1-3; 33% in s4-6; 10% in s7-9 and 0% in s10. After 30 days the sample was well distributed: 45% in s0; 36% in S1-3; 15% in s4-6; 4% in s7-9 and 0% in s10. CONCLUSIONS: The Low-Level-Laser-Therapy is a valuable tool that can significantly decrease the perception of pain in patients with temporomandibular joint dysfunction, acute and chronic.

11.
Oral Implantol (Rome) ; 10(4): 502-507, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29682268

RESUMO

BACKGROUND: The Obstructive Sleep Apnea Syndrome (OSAS) is a clinical picture characterized by partial or complete obstruction of the upper airway during sleep, associated with a reduction of oxygen saturation in the blood.The most common symptoms are: apnea sleep, snoring, headache, sleepiness, reduced concentration and memory, irritability, increased blood pressure and dry mouth. MATERIALS AND METHODS: It was examinated a not-smoker man of 54 years that suffers of roncophaty. He did physical examination, rhinoscopyexam, faringoscopy, rhinofibrolaringoscopy, gnathological evaluation and polysomnographic examination performed with multichannel polygraphy (VitalNight). From the performed examinations, it has been diagnosed a moderate form of obstructive apnea sleep syndrome. He was treated with a mandibular advancement device and it was repeated the polysomnographic exam. RESULTS: Comparing the results of the polysonographic examination performed before and after the treatment, the patient's clinical picture clearly improved. It has shown a clear reduction of obstructive apneas, hypopneas and snoring. CONCLUSIONS: The use of a mandibular advancement device is certainly a valuable aid in the treatment of moderate type OSAS. The quality of diurnal life is also improved as shown with Sleepness Epworth Scale.

12.
Nat Prod Res ; 30(2): 218-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26131916

RESUMO

The analysis of the polar fraction of Melittis melissophyllum L. subsp. melissophyllum led to the identification of several iridoid glycosides: monomelittoside (1), melittoside (2), harpagide (3), acetyl-harpagide (4) and ajugoside (5). Compounds 3 and 4 are considered marker compounds for the genus and, as well as compounds 1, 2 and 5, were already evidenced in a previous study on the nominal species. It was noteworthy of the presence of allobetonicoside (6) which was never reported for this genus. The isolation of 6 is very relevant because of its allose residue on the structure. Allose has been often found in the species of the subfamily Lamioideae even if it mostly regarded flavonoids considered of chemotaxonomical relevance for some correlated genera of Lamiaceae. Same as allosyl-glycosidic flavonoids, the presence of allosyl-glycosidic iridoids may also be an additional chemosystematic evidence of botanical relationships among Lamiaceae species and genera.


Assuntos
Iridoides/química , Lamiaceae/química , Glucosídeos/análise , Glicosídeos Iridoides/análise , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Iridoides/análise , Lamiaceae/classificação , Estrutura Molecular , Plantas Medicinais/química , Piranos/análise
13.
Oral Implantol (Rome) ; 9(4): 190-201, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28042448

RESUMO

The purpose of this text is to evaluate the distribution by sex and age of TMD patients and the frequency of pain on palpation of the lateral pterygoid muscle, pterygoid internal, sternocleidomastoid, masseter, temporal. The purpose is also to assess the existence of direct correlations between the articulating click and lateral deviation, the headache and tenderness of the temporal, the back pain and tenderness of the sternocleidomastoid, the postural disorders and difficulty finding the exact mating closing, the disorders related to previous dental procedures (large conservative reconstructions, rehabilitations fixed dentures and dental extractions) and tenderness to the temporal and masseter. 623 medical records, including 451 males and 175 females were randomly selected. It was statistically calculated the F/M ratio, age distribution and frequency of muscle tenderness to palpation through the relationship of positive feedback on the total sample multiplied by one hundred. The correlation between various disorders was calculated by estimating the Mantel-Haenszel common odds ratio. For each result it has been finally calculated the asymptotic level of significance.

14.
Nat Prod Res ; 30(9): 1098-102, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26508158

RESUMO

We analysed the ethanolic extract from Ajuga genevensis L. (Lamiaceae) growing in Dolomites, part of Italian Alps. Three new compounds for this species were identified: rosmarinic acid (1), oleanolic acid (2) and maslinic acid (3), representative of two different classes of chemical compounds (phenylpropanoids and pentacyclic triterpenes). A. genevensis resulted to be a valuable source of these compounds endowed with interesting biological activities (i.e. antioxidant, neuroprotective, anti-inflammatory, antiproliferative). The recognition of compounds (1), (2) and (3) may also confirm the ethnomedicinal uses of this plant. From a chemotaxonomical point of view, it is worth noting that iridoids were not evidenced in this accession. Iridoids are considered chemotaxonomic marker in Lamiales, and, in contrast with a previous study on this species, the presence of aucubin was not confirmed. In addition, the presence of large amounts of rosmarinic acid (1) was unexpected for a species that does not belong to subfamily Nepetoideae.


Assuntos
Ajuga/química , Extratos Vegetais/análise , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Cinamatos/análise , Depsídeos/análise , Glucosídeos Iridoides/análise , Iridoides/análise , Itália , Medicina Tradicional , Fármacos Neuroprotetores/farmacologia , Ácido Oleanólico/análise , Triterpenos/análise , Ácido Rosmarínico
15.
Nat Prod Res ; 30(14): 1665-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26675659

RESUMO

A re-examination of Scrophularia canina L. confirmed the presence of iridoid glucosides considered as chemotaxonomic markers for the Scrophulariaceae family, like aucubin, harpagide and 8-O-acetylharpagide, besides the further presence of 8-epiloganic acid, which is, indeed, considered the biogenetic precursor of iridoids normally found in Scrophulariaceae, and was recognised here for the first time in the studied species. Also verbascoside and (E)-phytol were evidenced for the first time in S. canina. The former compound is an almost ubiquitous glycosidic phenyl-ethanoid, which attains systematic importance when in co-occurrence with iridoids, and its taxonomical implications were discussed. The latter compound, even though it is omnipresent, is interestingly endowed with several biological activities, which may give an additional reason for the traditional uses of this plant.


Assuntos
Scrophularia/química , Classificação , Glucosídeos Iridoides/química , Glicosídeos Iridoides , Iridoides , Estrutura Molecular , Extratos Vegetais/química , Caules de Planta/química , Scrophularia/classificação
16.
Nat Prod Res ; 30(2): 185-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26222766

RESUMO

Digestate coming from an Anaerobic Digestion unit in a Biogas Plant, feeded on cow manure and vegetable waste from markets, has been used. About 8-35 L polyethylene transparent bags have been employed as cultivation container, outdoor. Different aliquots of digestate, alone or mixed with commercial liquid fertiliser, were employed to cultivate in batch Scenedesus dimorphus, a freshwater green microalga, in the ENEA facilities of Casaccia Research Center, near Rome, Italy. The cultivation period was June-July 2013. The average daily yields of dry microalgae biomass varied from 20 mg/L/d to 60 mg/L/d, mean 38.2 mg/L/d. Final dry biomass concentration varied from 0.18 to 1.29 g/L, mean 0.55 g/L. S. dimorphus proved to be very efficient in removing N and P from the culture medium. Another fact emerged from these trials is that S. dimorphus inner composition resulted to be variable in response to the tested different culture conditions.


Assuntos
Biocombustíveis , Fotobiorreatores , Scenedesmus/crescimento & desenvolvimento , Anaerobiose , Animais , Biomassa , Bovinos , Desenho de Equipamento , Feminino , Água Doce , Itália , Esterco , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Scenedesmus/metabolismo , Técnicas de Cultura de Tecidos/métodos
17.
Fitoterapia ; 113: 35-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27373875

RESUMO

Ajuga chamaepitys (L.) Schreb, well-known as Camaepitium or Ground Pine, is an annual herb typical of the Mediterranean area accounting several uses in the traditional medicine. In this work we have, analyzed the plant iridoid fraction together with the essential oil composition and study of the plant indumentum. Finally, we assayed the polar extracts and essential oil obtained from the aerial parts for antioxidant activity and cytotoxicity on tumor cells. The analysis of the monoterpene glycosides allowed us to isolate from roots and aerial parts and to structurally elucidate by NMR and MS the following compounds: ajugoside (1), reptoside (2), 8-O-acetylharpagide (3), harpagide (4), 5-O-ß-d-glucopyranosyl-harpagide (5), asperulosidic acid (6), deacetyl asperulosidic acid (7) and 5-O-ß-d-glucopyranosyl-8-O-acetylharpagide (8), among which 5 and 8 were two new natural products. Chemotaxomic relevance of these constituents was discussed. The chemical analysis of A. chamaepitys essential oil by GC-FID and GC-MS showed ethyl linoleate (13.7%), germacrene D (13.4%), kaurene (8.4%), ß-pinene (6.8%), and (E)-phytol (5.3%) as the major volatile components. The micromorphological and histochemical study showed that iridoids and essential oil are mainly produced in the type III capitates and peltate trichomes of leaves and flowers. Biological evaluations of A. chamaepitys polar extracts and essential oil showed that the former were more potent as radical scavengers than the latter. MTT assay revealed that essential oil and ethanolic extracts were moderately cytotoxic on tumor cells with IC50 of 36.88 and 59.24µg/mL on MDA-MB 231 cell line, respectively, and IC50 of 60.48 and 64.12µg/mL on HCT116, respectively.


Assuntos
Ajuga/química , Glicosídeos Iridoides/química , Óleos Voláteis/química , Óleos de Plantas/química , Piranos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Humanos , Glicosídeos Iridoides/isolamento & purificação , Extratos Vegetais/química , Piranos/isolamento & purificação , Tricomas/química , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação
18.
Drugs Today (Barc) ; 52(4): 249-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27252989

RESUMO

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Humanos , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia
19.
Leukemia ; 9(7): 1121-5, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7630182

RESUMO

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > or = 50%), was statistically significant (P < 0.001). Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to moderate hematologic toxicity was the most common side-effect. In conclusion all-trans retinoic acid and low-dose cytosine arabinoside appears to be an effective regimen for inducing complete remission in 'poor prognosis' acute myeloid leukemia and patients with < 50% bone marrow infiltration are likely to represent the ideal target to receive this combination therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos
20.
Leukemia ; 8(3): 388-94, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7907393

RESUMO

Clinical and cytologic characteristics were correlated to immunologic markers in 154 patients with newly diagnosed acute myeloid leukemia (AML). The panel of monoclonal antibodies (MoAbs) was selected to identify differentiation-associated antigens of both the myeloid and the lymphoid lineages (CD13, CD33, CD14, CD15, CD7, CD34, CD10, HLA-DR, CD19, CD2, CD5, TdT). The expression of multidrug resistance P-glycoprotein (P-170) was also evaluated in 117 patients. Differences in antigenic expression was observed among the various French-American-British (FAB) subgroups. HLA-DR was poorly expressed on the blasts of acute promyelocytic leukemia (M3), and was always found in FAB M5. CD34 was detectable in all M0 cases and only in one M3 (p < 0.001). Lymphoid-associated antigens were positive in 74 cases (48.1%). In particular, CD7 was found in 49 patients (31.8%), and TdT in 30 (21.3%), 15 samples displaying coexpression of these two antigens. The incidence of CD7+ cases was particularly elevated in M0 and M5 AML (p = 0.005). It significantly correlated with the expression of CD34, HLA-DR, P-170 (p < 0.001, p = 0.018 and p = 0.034 respectively), and with a leukocyte count > 50 x 10(9)/l (p = 0.038). Sixty-nine (59%) samples demonstrated P-170 positivity. Again, this phenotype was particularly expressed in the poorly differentiated forms (M5, M0 and M1) and showed significant correlation with the immaturity markers CD34, CD7 and HLA-DR (p = 0.013, p = 0.022 and p = 0.001, respectively). Expression of individual antigens correlated with prognosis. Refractoriness to first line therapy was associated with CD7 expression (p = 0.002) and P-170 (p = 0.001). The CD7 marker was also significantly associated with a very low overall survival (p < 0.001) and continuous complete remission (p < 0.001). CD14 expression also significantly predicted lower survival rates (p = 0.033). The combination (CD7+ CD14+) identified a subset of patients with a particularly adverse outcome. The prognostic value of CD7 expression, alone or in combination with other markers, was confirmed in multivariate analysis.


Assuntos
Antígenos CD/análise , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Biomarcadores Tumorais/análise , Leucemia Mieloide/imunologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/análise , DNA Nucleotidilexotransferase/análise , Feminino , Humanos , Imunofenotipagem , Leucemia Mieloide/classificação , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/mortalidade , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão
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