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  1. Article ; Online: Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors.

    Alves, Raquel / Pires, Ana / Jorge, Joana / Balça-Silva, Joana / Gonçalves, Ana Cristina / Sarmento-Ribeiro, Ana Bela

    International journal of molecular sciences

    2024  Volume 25, Issue 8

    Abstract: The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment ... ...

    Abstract The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.
    MeSH term(s) Humans ; Apoptosis/drug effects ; Hematologic Neoplasms/drug therapy ; Hematologic Neoplasms/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Antineoplastic Agents/pharmacology ; Cytostatic Agents/pharmacology ; Cell Proliferation/drug effects ; Hydroxamic Acids/pharmacology ; Hydroxamic Acids/therapeutic use ; HL-60 Cells ; Matrix Metalloproteinase Inhibitors/pharmacology ; Cell Cycle Checkpoints/drug effects ; MAP Kinase Signaling System/drug effects ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/pathology ; Phenylalanine/analogs & derivatives ; Thiophenes
    Chemical Substances batimastat (BK349F52C9) ; Antineoplastic Agents ; Cytostatic Agents ; Hydroxamic Acids ; Matrix Metalloproteinase Inhibitors ; Phenylalanine (47E5O17Y3R) ; Thiophenes
    Language English
    Publishing date 2024-04-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25084554
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies.

    Jorge, Joana / Neves, Joana / Alves, Raquel / Geraldes, Catarina / Gonçalves, Ana Cristina / Sarmento-Ribeiro, Ana Bela

    International journal of molecular sciences

    2023  Volume 24, Issue 11

    Abstract: Lymphoid malignancies are a group of highly heterogeneous diseases frequently associated with constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway. Parthenolide is a natural compound used to treat migraines and arthritis and ... ...

    Abstract Lymphoid malignancies are a group of highly heterogeneous diseases frequently associated with constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway. Parthenolide is a natural compound used to treat migraines and arthritis and found to act as a potent NF-κB signaling inhibitor. This study evaluated in vitro parthenolide efficacy in lymphoid neoplasms. We assessed parthenolide metabolic activity in NCI-H929 (MM), Farage (GCB-DLBCL), Raji (BL), 697 and KOPN-8 (B-ALL), and CEM and MOLT-4 (T-ALL), by resazurin assay. Cell death, cell cycle, mitochondrial membrane potential (ΔΨ
    MeSH term(s) Humans ; NF-kappa B/metabolism ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Apoptosis ; Sesquiterpenes/pharmacology ; I-kappa B Proteins ; Lymphoma/drug therapy
    Chemical Substances NF-kappa B ; Reactive Oxygen Species ; parthenolide (2RDB26I5ZB) ; Sesquiterpenes ; I-kappa B Proteins
    Language English
    Publishing date 2023-05-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24119167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation.

    Jorge, Joana / Magalhães, Nisa / Alves, Raquel / Lapa, Beatriz / Gonçalves, Ana Cristina / Sarmento-Ribeiro, Ana Bela

    Biomedicines

    2022  Volume 10, Issue 9

    Abstract: Acute lymphoblastic leukemia (ALL) is one of the most common hematological malignancies at pediatric ages and is characterized by different chromosomal rearrangements and genetic abnormalities involved in the differentiation and proliferation of lymphoid ...

    Abstract Acute lymphoblastic leukemia (ALL) is one of the most common hematological malignancies at pediatric ages and is characterized by different chromosomal rearrangements and genetic abnormalities involved in the differentiation and proliferation of lymphoid precursor cells. Brusatol is a quassinoid plant extract extensively studied due to its antineoplastic effect through global protein synthesis and nuclear factor erythroid 2-related factor-2 (NRF2) signaling inhibition. NRF2 is the main regulator of cellular antioxidant response and reactive oxygen species (ROS), which plays an important role in oxidative stress regulation. This study aimed to evaluate the effect of brusatol in in vitro models of ALL. KOPN-8 (B-ALL), CEM (T-ALL), and MOLT-4 (T-ALL) cell lines were incubated with increasing concentrations of brusatol, and the metabolic activity was evaluated using the resazurin assay. Flow cytometry was used to evaluate cell death, cell cycle, mitochondrial membrane potential (Δψ
    Language English
    Publishing date 2022-09-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10092207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Combination of Elacridar with Imatinib Modulates Resistance Associated with Drug Efflux Transporters in Chronic Myeloid Leukemia.

    Alves, Raquel / Gonçalves, Ana Cristina / Jorge, Joana / Almeida, António M / Sarmento-Ribeiro, Ana Bela

    Biomedicines

    2022  Volume 10, Issue 5

    Abstract: Multidrug resistance (MDR) development has emerged as a complication that compromises the success of several chemotherapeutic agents. In chronic myeloid leukemia (CML), imatinib resistance has been associated with changes ... ...

    Abstract Multidrug resistance (MDR) development has emerged as a complication that compromises the success of several chemotherapeutic agents. In chronic myeloid leukemia (CML), imatinib resistance has been associated with changes in
    Language English
    Publishing date 2022-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10051158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Alvespimycin Inhibits Heat Shock Protein 90 and Overcomes Imatinib Resistance in Chronic Myeloid Leukemia Cell Lines.

    Alves, Raquel / Santos, Diogo / Jorge, Joana / Gonçalves, Ana Cristina / Catarino, Steve / Girão, Henrique / Melo, Joana Barbosa / Sarmento-Ribeiro, Ana Bela

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 3

    Abstract: Heat shock protein 90 (HSP90) facilitates folding and stability and prevents the degradation of multiple client proteins. One of these HSP90 clients is BCR-ABL, the oncoprotein characteristic of chronic myeloid leukemia (CML) and the target of tyrosine ... ...

    Abstract Heat shock protein 90 (HSP90) facilitates folding and stability and prevents the degradation of multiple client proteins. One of these HSP90 clients is BCR-ABL, the oncoprotein characteristic of chronic myeloid leukemia (CML) and the target of tyrosine kinase inhibitors, such as imatinib. Alvespimycin is an HSP90 inhibitor with better pharmacokinetic properties and fewer side effects than other similar drugs, but its role in overcoming imatinib resistance is not yet clarified. This work studied the therapeutic potential of alvespimycin in imatinib-sensitive (K562) and imatinib-resistant (K562-RC and K562-RD) CML cell lines. Metabolic activity was determined by the resazurin assay. Cell death, caspase activity, mitochondrial membrane potential, and cell cycle were evaluated by means of flow cytometry. Cell death was also analyzed by optical microscopy. HSPs expression levels were assessed by western blotting. Alvespimycin reduced metabolic activity in a time-, dose-, and cell line-dependent manner. Resistant cells were more sensitive to alvespimycin with an IC
    MeSH term(s) Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Heat-Shock Proteins ; Imatinib Mesylate/pharmacology ; Imatinib Mesylate/therapeutic use ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; HSP90 Heat-Shock Proteins/metabolism
    Chemical Substances 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (001L2FE0M3) ; Antineoplastic Agents ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Heat-Shock Proteins ; Imatinib Mesylate (8A1O1M485B) ; HSP90 Heat-Shock Proteins
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28031210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Platelet Membrane Proteins as Pain Biomarkers in Patients with Severe Dementia.

    Ribeiro, Hugo / Alves, Raquel / Jorge, Joana / Gonçalves, Ana Cristina / Sarmento-Ribeiro, Ana Bela / Teixeira-Veríssimo, Manuel / Dourado, Marília / Andrade, José Paulo

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: Pain is one of the most frequent health problems, and its evaluation and therapeutic approach largely depend on patient self-report. When it is not possible to obtain a self-report, the therapeutic decision becomes more difficult and limited. This study ... ...

    Abstract Pain is one of the most frequent health problems, and its evaluation and therapeutic approach largely depend on patient self-report. When it is not possible to obtain a self-report, the therapeutic decision becomes more difficult and limited. This study aims to evaluate whether some membrane platelet proteins could be of value in pain characterization. To achieve this goal, we used 53 blood samples obtained from palliative patients, 44 with non-oncological pain and nine without pain. We observed in patients with pain a decrease in the percentage of platelets expressing CD36, CD49f, and CD61 and in the expression levels of CD49f and CD61 when compared with patients without pain. Besides that, an increase in the percentage of platelets expressing CD62p was observed in patients with pain. These results suggest that the levels of these platelet cluster differentiations (CDs) could have some value as pain biomarkers objectively since they are not dependent on the patient's participation. Likewise, CD40 seems to have some importance as a biomarker of moderate and/or severe pain. The identification of pain biomarkers such as CD40, CD49f, CD62p and CD61 can lead to an adjustment of the therapeutic strategy, contributing to a faster and more adequate control of pain and reduction in patient-associated suffering.
    Language English
    Publishing date 2023-01-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020380
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Monocytes in the Characterization of Pain in Palliative Patients with Severe Dementia-A Pilot Study.

    Ribeiro, Hugo / Alves, Raquel / Jorge, Joana / Gonçalves, Ana Cristina / Sarmento-Ribeiro, Ana Bela / Teixeira-Veríssimo, Manuel / Andrade, José Paulo / Dourado, Marília

    International journal of molecular sciences

    2023  Volume 24, Issue 13

    Abstract: In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of ... ...

    Abstract In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of differentiation (CD), could be potential non-invasive peripheral biomarkers in identifying and characterizing pain in patients with severe dementia. We used 53 blood samples from non-oncological palliative patients, 44 patients with pain (38 of whom had dementia) and 0 without pain or dementia (controls). We evaluated the levels of monocytes and their subtypes, including classic, intermediate, and non-classic, and characterized the levels of specific phenotypic markers, namely CD11c, CD86, CD163, and CD206. We found that the relative concentrations of monocytes, particularly the percentage of classic monocytes, may be a helpful pain biomarker. Furthermore, the CD11c expression levels were significantly higher in patients with mixed pain, while CD163 and CD206 expression levels were significantly higher in patients with nociceptive pain. These findings suggest that the levels of monocytes, particularly the classic subtype, and their phenotype markers CD11c, CD163, and CD206 could serve as pain biomarkers in patients with severe dementia.
    MeSH term(s) Humans ; Monocytes/metabolism ; Pilot Projects ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers/metabolism ; Membrane Proteins/metabolism ; Pain/metabolism ; Dementia/complications ; Dementia/metabolism
    Chemical Substances Antigens, Differentiation, Myelomonocytic ; Biomarkers ; Membrane Proteins
    Language English
    Publishing date 2023-06-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241310723
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells.

    Costa, Maria Inês / Lapa, Beatriz Santos / Jorge, Joana / Alves, Raquel / Carreira, Isabel Marques / Sarmento-Ribeiro, Ana Bela / Gonçalves, Ana Cristina

    International journal of molecular sciences

    2022  Volume 23, Issue 5

    Abstract: Genomic instability is prevented by the DNA damage response (DDR). Micronutrients, like zinc (Zn), are cofactors of DDR proteins, and micronutrient deficiencies have been related to increased cancer risk. Acute myeloid leukemia (AML) patients commonly ... ...

    Abstract Genomic instability is prevented by the DNA damage response (DDR). Micronutrients, like zinc (Zn), are cofactors of DDR proteins, and micronutrient deficiencies have been related to increased cancer risk. Acute myeloid leukemia (AML) patients commonly present Zn deficiency. Moreover, reports point to DDR defects in AML. We studied the effects of Zn in DDR modulation in AML. Cell lines of AML (HEL) and normal human lymphocytes (IMC) were cultured in standard culture, Zn depletion, and supplementation (40 μM ZnSO
    MeSH term(s) Antineoplastic Agents ; DNA Damage ; Humans ; Hydrogen Peroxide/toxicity ; Leukemia, Myeloid, Acute/genetics ; Micronucleus Tests ; Zinc/pharmacology
    Chemical Substances Antineoplastic Agents ; Hydrogen Peroxide (BBX060AN9V) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2022-02-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23052567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Urate-lowering effect of calcium supplementation: Analyses of a randomized controlled trial.

    Cândido, Flávia Galvão / Alves, Raquel Duarte Moreira / Freitas, Dayse Mara de Oliveira / Bittencourt, Jersica Martins / Rocha, Daniela Mayumi Usuda Prado / Alfenas, Rita de Cássia Gonçalves

    Clinical nutrition ESPEN

    2022  Volume 49, Page(s) 86–91

    Abstract: Objective: To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium.: Methods: This is a placebo-controlled trial in which thirty-five adult (aged 18-42 years) female low- ... ...

    Abstract Objective: To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium.
    Methods: This is a placebo-controlled trial in which thirty-five adult (aged 18-42 years) female low-calcium consumers (<800 mg/d) were randomized to one of three treatment groups: low calcium breakfast (control, ∼70 mg of calcium/d) -C or high-calcium breakfast (∼770 mg/d) from calcium citrate - CIT or from skim milk - SM, during 45 consecutive days. Breakfasts were matched for potential confounders and were provided as part of an energy-restricted normoprotein diet containing an additional 800 mg of calcium/d. Dual-energy X-ray absorptiometry measurements (body fat assessment) and fasting blood samples (urate, ionic calcium, PTH, and 1,25-(OH)2-D3) were taken at baseline and the end of the experiment.
    Clinical trial registration: http://www.ensaiosclinicos.gov.br/ (RBR-7Q2N33).
    Results: Despite no significant changes in total body weight/fat, CIT and SM led to a significant reduction in serum urate and ionic calcium, but did not affect PTH and vitamin D concentrations compared to C. CIT and SM reduced baseline serum urate by ∼14% and ∼17%, respectively. There was a trend to a positive correlation between changes in serum urate and changes in ionic calcium on day 45 (r = 0.327, P = 0.055).
    Conclusions: Calcium supplementation (770 mg/d from dairy or calcium citrate) reduced serum urate concentrations, suggesting that the gout-protective effect of low-fat dairy consumption is at least partly due to a urate-lowering effect of calcium.
    MeSH term(s) Adult ; Calcium ; Calcium Citrate/pharmacology ; Calcium, Dietary ; Dietary Supplements ; Female ; Gout ; Humans ; Uric Acid
    Chemical Substances Calcium, Dietary ; Uric Acid (268B43MJ25) ; Calcium Citrate (MLM29U2X85) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-03-09
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2405-4577
    ISSN (online) 2405-4577
    DOI 10.1016/j.clnesp.2022.02.121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Urate-lowering effect of calcium supplementation: Analyses of a randomized controlled trial

    Cândido, Flávia Galvão / Alves, Raquel Duarte Moreira / Freitas, Dayse Mara de Oliveira / Bittencourt, Jersica Martins / Rocha, Daniela Mayumi Usuda Prado / Alfenas, Rita de Cássia Gonçalves

    European Society for Clinical Nutrition and Metabolism Clinical Nutrition ESPEN. 2022 June, v. 49 p.86-91

    2022  

    Abstract: To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium. This is a placebo-controlled trial in which thirty-five adult (aged 18–42 years) female low-calcium consumers (<800 mg/d) ... ...

    Abstract To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium. This is a placebo-controlled trial in which thirty-five adult (aged 18–42 years) female low-calcium consumers (<800 mg/d) were randomized to one of three treatment groups: low calcium breakfast (control, ∼70 mg of calcium/d) –C or high-calcium breakfast (∼770 mg/d) from calcium citrate – CIT or from skim milk – SM, during 45 consecutive days. Breakfasts were matched for potential confounders and were provided as part of an energy-restricted normoprotein diet containing an additional 800 mg of calcium/d. Dual-energy X-ray absorptiometry measurements (body fat assessment) and fasting blood samples (urate, ionic calcium, PTH, and 1,25-(OH)2-D3) were taken at baseline and the end of the experiment. Clinical trial registration: http://www.ensaiosclinicos.gov.br/ (RBR-7Q2N33). Despite no significant changes in total body weight/fat, CIT and SM led to a significant reduction in serum urate and ionic calcium, but did not affect PTH and vitamin D concentrations compared to C. CIT and SM reduced baseline serum urate by ∼14% and ∼17%, respectively. There was a trend to a positive correlation between changes in serum urate and changes in ionic calcium on day 45 (r = 0.327, P = 0.055). Calcium supplementation (770 mg/d from dairy or calcium citrate) reduced serum urate concentrations, suggesting that the gout-protective effect of low-fat dairy consumption is at least partly due to a urate-lowering effect of calcium.
    Keywords adults ; blood serum ; body fat ; body weight ; breakfast ; calcium ; calcium citrate ; clinical nutrition ; dairy consumption ; dual-energy X-ray absorptiometry ; females ; low fat dairy products ; randomized clinical trials ; skim milk ; Dairy products ; Milky ; PTH ; Vitamin D ; Uricemia ; LC ; CIT ; SM
    Language English
    Dates of publication 2022-06
    Size p. 86-91.
    Publishing place Elsevier Ltd
    Document type Article ; Online
    ISSN 2405-4577
    DOI 10.1016/j.clnesp.2022.02.121
    Database NAL-Catalogue (AGRICOLA)

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