Publications by authors named "Ana L M Batista de Carvalho"

Article Synopsis
  • The study evaluated how human osteosarcoma cells respond to the chemotherapy drug cisplatin using advanced nanospectroscopy techniques at a specialized research facility in the UK.
  • The method used, synchrotron-based Fourier Transform InfraRed nanospectroscopy, allowed researchers to analyze the cells at a very small scale (hundreds of nanometers), providing detailed information about both the structure and biochemical changes occurring in the cells.
  • Results indicated that cisplatin significantly impacted proteins and cellular lipids, with a notable concentration of these effects occurring in the cytoplasm, marking a pioneering application of this nanospectroscopy technique in cancer research.
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  • * This study evaluated the effects of new palladium-based complexes linked to polyamines (spermine and spermidine) on both non-cancerous and osteosarcoma cell lines, comparing them to the standard drug, cisplatin.
  • * Advanced microspectroscopies were utilized to analyze the drugs' impact on cellular metabolism, revealing distinct changes in DNA conformation and protein content, which demonstrated the effectiveness of combined drug treatments under the EURAMOS-1 protocol.
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Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to PdSpermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of PdSpm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites.

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  • * To reduce mortality, it's essential to develop new methods for reliable screening and early diagnosis of cervical lesions.
  • * Vibrational spectroscopy, especially Fourier transform infrared microspectroscopy, has shown promising results in diagnosing tumors and achieved over 90% accuracy in classifying cryopreserved cervical tissue samples using machine learning.
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This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug PdSpermine (Spm) and its Pt(II) analog, against osteosarcoma MG-63 cells, using nuclear-magnetic-resonance metabolomics of the cellular lipidome. The Pt(II) chelates induced different responses, namely regarding polyunsaturated-fatty-acids (increased upon cisplatin), suggesting that cisplatin-treated cells have higher membrane fluidity/permeability, thus facilitating cell entry and justifying higher cytotoxicity. Both conventional drugs significantly increased triglyceride levels, while PtSpm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for PtSpm.

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A new fluorinated manganese porphyrin, (Mn-TPP-p-CF ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual H relaxivity and F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d /H O evidenced that the H relaxometric and F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (d =9.

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Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer and constitutes 10-20% of all breast cancer cases. Even though platinum-based drugs such as cisplatin and carboplatin are effective in TNBC patients, their toxicity and development of cancer drug resistance often hamper their clinical use. Hence, novel drug entities with improved tolerability and selectivity profiles, as well as the ability to surpass resistance, are needed.

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A dinuclear Pt(II) complex with putrescine as bridging polyamine ligand ([PtPut(NH)]Cl) was synthesized and assessed as to its potential anticancer activity against a human non-small cell lung cancer line (A549), as well as towards non-cancer cells (BEAS-2B). This effect was evaluated through in vitro cytotoxicity assays (MTT and SRB) coupled to microFTIR and microRaman spectroscopies, the former delivering information on growth-inhibiting and cytotoxic abilities while the latter provided very specific information on the metabolic impact of the metal agent (at the sub-cellular level). Regarding cancer cells, a major impact of [PtPut(NH)]Cl was evidenced on cellular proteins and lipids, as compared to DNA, particularly via the Amide I and Amide II signals.

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Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (PdSpm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and PdSpm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used.

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Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound PdSpermine (PdSpm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to PdSpm, compared to cDDP, and (ii) correlate brain-liver metabolic variations.

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Breast cancer is a type of cancer with the highest incidence worldwide in 2021, with early diagnosis and rapid treatment intervention being the reasons for the decreasing mortality rate associated with the disease. The major challenge faced by clinicians and pathologists is the lack of accuracy in the histopathological analysis of biopsy or resection samples, leading to classification misdiagnosis and compromising the prognosis of patients. Spectral histopathology has provided great advances regarding cancer diagnosis, especially through the use of FTIR spectroscopy, proving to be a valuable complement to histopathological analyses.

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The new palladium agent PdSpermine (Spm) has been reported to exhibit promising cytotoxic properties, while potentially circumventing the known disadvantages associated to cisplatin therapeutics, namely acquired resistance and high toxicity. This work presents a nuclear magnetic resonance (NMR) metabolomics study of brain extracts obtained from healthy mice, to assess the metabolic impacts of the new PdSpm complex in comparison to that of cisplatin. The proton NMR spectra of both polar and nonpolar brain extracts were analyzed by multivariate and univariate statistics, unveiling several metabolite variations during the time course of exposition to each drug (1-48 h).

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PdSpm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of PdSpm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies.

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Article Synopsis
  • Breast cancer is the leading cause of death among women globally, and this study focuses on finding molecular biomarkers to distinguish aggressive triple-negative breast cancer (TNBC) from non-TNBC and different TNBC subtypes for better patient care.
  • Advanced techniques like Raman and FTIR microspectroscopy were used as non-invasive methods to analyze human breast cancer cells, enabling detailed examination of their biochemical characteristics.
  • The research identified specific vibrational signatures of cancer cells through principal component analysis, allowing for the differentiation of various TNBC subtypes, which could significantly enhance cancer diagnosis and treatment strategies.
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In 2020, approximately 10 million people died of cancer, rendering this disease the second leading cause of death worldwide. Detecting cancer in its early stages is paramount for patients' prognosis and survival. Hence, the scientific and medical communities are engaged in improving both therapeutic strategies and diagnostic methodologies, beyond prevention.

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Caco-2 monolayers are a common in vitro model used to evaluate human intestinal absorption. The reference protocol requires 21 days post-seeding to establish a stable and confluent cell monolayer, which is used in a single permeability assay during the period of monolayer stability (up to day 30). In this work, we characterize variations in the tightness of the cell monolayer over the stable time interval and evaluate the conditions required for their re-use in permeability assays.

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The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g.

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This paper reports the first metabolomics study of the impact of new chelates PtSpm and PdSpm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the effects of different metal centers and ligands. Nuclear Magnetic Resonance metabolomics was used to identify meaningful metabolite variations in polar cell extracts collected during exposure to each of the four chelates. Cisplatin and oxaliplatin induced similar metabolic fingerprints of changing metabolite levels (affecting many amino acids, organic acids, nucleotides, choline compounds and other compounds), thus suggesting similar mechanisms of action.

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This experimental work applied coherent synchrotron-radiation terahertz spectroscopy and inelastic neutron scattering to address two processes directly associated with the mode of action of metal-based anticancer agents that can severely undermine chemotherapeutic treatment: drug binding to human serum albumin, occurring during intravenous drug transport, and intracellular coordination to thiol-containing biomolecules (such as metallothioneins) associated with acquired drug resistance. Cisplatin and two dinuclear platinum (Pt)- and palladium (Pd)-polyamine agents developed by this research group, which have yielded promising results toward some types of human cancers, were investigated. Complementary synchrotron-radiation-terahertz and inelastic neutron scattering data revealed protein metalation, through S- and N-donor ligands from cysteine, methionine, and histidine residues.

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Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (PdSpm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of PdSpm (3 mg/kg bw) or cisplatin (3.

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Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance.

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The mode of action of Pt- and Pd-based anticancer agents (cisplatin and PdSpm) was studied by characterising their impact on DNA. Changes in conformation and mobility at the molecular level in hydrated DNA were analysed by quasi-elastic and inelastic neutron scattering techniques (QENS and INS), coupled to Fourier transform infrared (FTIR) and microRaman spectroscopies. Although INS, FTIR and Raman revealed drug-triggered changes in the phosphate groups and the double helix base pairing, QENS allowed access to the nanosecond motions of the biomolecule's backbone and confined hydration water within the minor groove.

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This work describes, to our knowledge, the first NMR metabolomics analysis of mice kidney, liver, and breast tissue in response to cisplatin exposure, in search of early metabolic signatures of cisplatin biotoxicity. Balb/c mice were exposed to a single 3.5 mg/kg dose of cisplatin and then euthanized; organs (kidney, liver, breast tissue) were collected at 1, 12, and 48 h.

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This study aimed at the development of improved drugs against human osteosarcoma, which is the most common primary bone tumor in children and teenagers with a low prognosis. New insights into the impact of an unconventional Pd(II) anticancer agent on human osteosarcoma cells were obtained by synchrotron radiation-Fourier transform infrared microspectroscopy and quasi-elastic neutron scattering (QENS) experiments from its effect on the cellular metabolism to its influence on intracellular water, which can be regarded as a potential secondary pharmacological target. Specific infrared biomarkers of drug action were identified, enabling a molecular-level description of variations in cellular biochemistry upon drug exposure.

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Complementary structural and dynamical information on drug-DNA interplay has been achieved at a molecular level, for Pt/Pd-drugs, allowing a better understanding of their pharmacodynamic profile which is crucial for the development of improved chemotherapeutic agents. The interaction of two cisplatin-like dinuclear Pt(ii) and Pd(ii) complexes with DNA was studied through a multidisciplinary experimental approach, using quasi-elastic neutron scattering (QENS) techniques coupled with synchrotron-based extended X-ray absorption fine structure (SR-EXAFS) and Fourier-Transform Infrared Spectroscopy-Attenuated Total Reflectance (SR-FTIR-ATR). DNA extracted from drug-exposed human triple negative breast cancer cells (MDA-MB-231) was used, with a view to evaluate the effect of the unconventional antineoplastic agents on this low prognosis type of cancer.

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