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3. Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients

Author

Heath Jeffery, Rachael C., primary, Thompson, Jennifer A., additional, Lo, Johnny, additional, Chelva, Enid S., additional, Armstrong, Sean, additional, Pulido, Jose S., additional, Procopio, Rebecca, additional, Vincent, Andrea L., additional, Bianco, Lorenzo, additional, Battaglia Parodi, Maurizio, additional, Ziccardi, Lucia, additional, Antonelli, Giulio, additional, Barbano, Lucilla, additional, Marques, João P., additional, Geada, Sara, additional, Carvalho, Ana L., additional, Tang, Wei C., additional, Chan, Choi M., additional, Boon, Camiel J. F., additional, Hensman, Jonathan, additional, Chen, Ta-Ching, additional, Lin, Chien-Yu, additional, Chen, Pei-Lung, additional, Vincent, Ajoy, additional, Tumber, Anupreet, additional, Heon, Elise, additional, Grigg, John R., additional, Jamieson, Robyn V., additional, Cornish, Elisa E., additional, Nash, Benjamin M., additional, Borooah, Shyamanga, additional, Ayton, Lauren N., additional, Britten-Jones, Alexis Ceecee, additional, Edwards, Thomas L., additional, Ruddle, Jonathan B., additional, Sharma, Abhishek, additional, Porter, Rowan G., additional, Lamey, Tina M., additional, McLaren, Terri L., additional, McLenachan, Samuel, additional, Roshandel, Danial, additional, and Chen, Fred K., additional

Published
2024
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5. Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients

Author

Heath Jeffery, Rachael C., Thompson, Jennifer A., Lo, Johnny, Chelva, Enid S., Armstrong, Sean, Pulido, Jose S., Procopio, Rebecca, Vincent, Andrea L., Bianco, Lorenzo, Battaglia Parodi, Maurizio, Ziccardi, Lucia, Antonelli, Giulio, Barbano, Lucilla, Marques, João P., Geada, Sara, Carvalho, Ana L., Tang, Wei C., Chan, Choi M., Boon, Camiel J. F., Hensman, Jonathan, Chen, Ta-Ching, Lin, Chien-Yu, Chen, Pei-Lung, Vincent, Ajoy, Tumber, Anupreet, Heon, Elise, Grigg, John R., Jamieson, Robyn V., Cornish, Elisa E., Nash, Benjamin M., Borooah, Shyamanga, Ayton, Lauren N., Britten-Jones, Alexis Ceecee, Edwards, Thomas L., Ruddle, Jonathan B., Sharma, Abhishek, Porter, Rowan G., Lamey, Tina M., McLaren, Terri L., McLenachan, Samuel, Roshandel, Danial, Chen, Fred K., Heath Jeffery, Rachael C., Thompson, Jennifer A., Lo, Johnny, Chelva, Enid S., Armstrong, Sean, Pulido, Jose S., Procopio, Rebecca, Vincent, Andrea L., Bianco, Lorenzo, Battaglia Parodi, Maurizio, Ziccardi, Lucia, Antonelli, Giulio, Barbano, Lucilla, Marques, João P., Geada, Sara, Carvalho, Ana L., Tang, Wei C., Chan, Choi M., Boon, Camiel J. F., Hensman, Jonathan, Chen, Ta-Ching, Lin, Chien-Yu, Chen, Pei-Lung, Vincent, Ajoy, Tumber, Anupreet, Heon, Elise, Grigg, John R., Jamieson, Robyn V., Cornish, Elisa E., Nash, Benjamin M., Borooah, Shyamanga, Ayton, Lauren N., Britten-Jones, Alexis Ceecee, Edwards, Thomas L., Ruddle, Jonathan B., Sharma, Abhishek, Porter, Rowan G., Lamey, Tina M., McLaren, Terri L., McLenachan, Samuel, Roshandel, Danial, and Chen, Fred K.

Abstract

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Published
2024

8. A case of larva migrans representing a pitfall in oral diagnosis.

Author

Koth, Valesca S., Salum, Fernanda G., de Carvalho, Ana L. H., Maito, Fábio L. D., Payeras, Marcia, and Cherubini, Karen

Subjects
MEDICAL personnel, ORAL mucosa, NEMATODE infections, DIFFERENTIAL diagnosis, LARVAE
Abstract

The present work reports a case of a female patient complaining of itching and painful lesions affecting the oral mucosa for 7 months. Buccal and lip mucosa showed swelling and erythema, with serpiginous tracks. The patient was diagnosed with oral larva migrans, and the lesions resolved after ivermectin administration. At 18-month follow-up, no sign of recurrence was observed. Larva migrans can represent a pitfall in oral diagnosis and a stressful condition for the patient. Oral health care providers should be aware of this and keep this disease in mind as a possible differential diagnosis in oral mucosa lesions. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Extracellular vesicles produced by the human gut commensal bacterium Bacteroides thetaiotaomicron elicit anti-inflammatory responses from innate immune cells.

Author

Fonseca, Sonia, Carvalho, Ana L., Miquel-Clopés, Ariadna, Jones, Emily J., Juodeikis, Rokas, Stentz, Régis, and Carding, Simon R.

Subjects
EXTRACELLULAR vesicles, BACTEROIDES, BONE marrow, WEIGHT loss, DEXTRAN sulfate, SODIUM sulfate
Abstract

Bacterial extracellular vesicles (BEVs) produced by gut commensal bacteria have been proposed to play an important role in maintaining host homeostasis via interactions with the immune system. Details of the mediators and pathways of BEV-immune cell interactions are however incomplete. In this study, we provide evidence for the anti-inflammatory and immunomodulatory properties of extracellular vesicles produced by the prominent human gut commensal bacterium Bacteroides thetaiotaomicron (Bt BEVs) and identify the molecular mechanisms underlying their interaction with innate immune cells. In mice treated with colitis-inducing dextran sodium sulfate (DSS) there was some indication that Bt BEVs improved survival, weight loss, disease activity and increased IL-10 production. Pre-treatment (conditioning) of murine bone marrow derived monocytes (BMDM) with Bt BEVs resulted in higher ratio of IL-10/TNFα production after an LPS challenge when compared to LPS preconditioned or non-conditioned BMDM. Using the THP-1 monocytic cell line the interactions between Bt BEVs and monocytes/macrophages were shown to be mediated primarily by TLR2. Histone (H3K4me1) methylation analysis showed that Bt BEVs induced epigenetic reprogramming which persisted after infectious challenge, as revealed by increased levels of H3K4me1 in Bt BEVconditioned LPS-challenged BMDM. Collectively, our findings highlight the important role of Bt BEVs in maintaining host immune homeostasis and raise the promising possibility of considering their use in immune therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Evaluation of the Cytotoxic Effect of Pd 2 Spm against Prostate Cancer through Vibrational Microspectroscopies.

Author

Laginha, Raquel C., Martins, Clara B., Brandão, Ana L. C., Marques, Joana, Marques, M. Paula M., Batista de Carvalho, Luís A. E., Santos, Inês P., and Batista de Carvalho, Ana L. M.

Subjects
POLYAMINES, PROSTATE cancer, ANTINEOPLASTIC agent development, PRINCIPAL components analysis, CELL lines, CISPLATIN
Abstract

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 (Pd2Spm) 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 Pd2Spm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Pd2Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice

Author

Vojtek, Martin, primary, Gonçalves-Monteiro, Salomé, additional, Šeminská, Patrícia, additional, Valová, Katarína, additional, Bellón, Loreto, additional, Dias-Pereira, Patrícia, additional, Marques, Franklim, additional, Marques, Maria P. M., additional, Batista de Carvalho, Ana L. M., additional, Mota-Filipe, Helder, additional, Ferreira, Isabel M. P. L. V. O., additional, and Diniz, Carmen, additional

Published
2022
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21. Effect of Pd 2 Spermine on Mice Brain-Liver Axis Metabolism Assessed by NMR Metabolomics.

Author

Carneiro, Tatiana J., Vojtek, Martin, Gonçalves-Monteiro, Salomé, Batista de Carvalho, Ana L. M., Marques, Maria Paula M., Diniz, Carmen, and Gil, Ana M.

Subjects
METABOLOMICS, SPERMINE, NUCLEAR magnetic resonance, LIVER regeneration, POLYAMINES, METABOLISM, MICE
Abstract

Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound Pd2Spermine (Pd2Spm) 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 Pd2Spm, compared to cDDP, and (ii) correlate brain-liver metabolic variations. Multivariate and correlation analysis of the spectra of polar and lipophilic brain and liver extracts from an MDA-MB-231 cell-derived mouse model revealed a stronger impact of Pd2Spm on brain metabolome, compared to cDDP. This was expressed by changes in amino acids, inosine, cholate, pantothenate, fatty acids, phospholipids, among other compounds. Liver was less affected than brain, with cDDP inducing more metabolite changes. Results suggest that neither drug induces neuronal damage or inflammation, and that Pd2Spm seems to lead to enhanced brain anti-inflammatory and antioxidant mechanisms, regulation of brain bioactive metabolite pools and adaptability of cell membrane characteristics. The cDDP appears to induce higher extension of liver damage and an enhanced need for liver regeneration processes. This work demonstrates the usefulness of untargeted metabolomics in evaluating drug impact on multiple organs, while confirming Pd2Spm as a promising replacement of cDDP. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Additional file 2 of Regulation of blood���brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

Author

Hoyles, Lesley, Pontifex, Matthew G., Rodriguez-Ramiro, Ildefonso, Anis-Alavi, M. Areeb, Jelane, Khadija S., Snelling, Tom, Solito, Egle, Fonseca, Sonia, Carvalho, Ana L., Carding, Simon R., M��ller, Michael, Glen, Robert C., Vauzour, David, and McArthur, Simon

Abstract

Additional file 1: Supplementary Figures 1-4

Published
2021
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28. Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice

Author

Vojtek, Martin, primary, Gonçalves-Monteiro, Salomé, additional, Pinto, Edgar, additional, Kalivodová, Sára, additional, Almeida, Agostinho, additional, Marques, Maria P. M., additional, Batista de Carvalho, Ana L. M., additional, Martins, Clara B., additional, Mota-Filipe, Helder, additional, Ferreira, Isabel M. P. L. V. O., additional, and Diniz, Carmen, additional

Published
2021
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33. Chemotherapeutic Targets in Osteosarcoma: Insights from Synchrotron-MicroFTIR and Quasi-Elastic Neutron Scattering

Author

Marques, Maria Paula M., primary, Batista de Carvalho, Ana L. M., additional, Mamede, Adriana P., additional, Santos, Inês P., additional, García Sakai, Victoria, additional, Dopplapudi, Asha, additional, Cinque, Gianfelice, additional, Wolna, Magda, additional, Gardner, Peter, additional, and Batista de Carvalho, Luís A. E., additional

Published
2019
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34. Bioengineering commensal bacteria‐derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract

Author

Carvalho, Ana L., primary, Fonseca, Sonia, additional, Miquel‐Clopés, Ariadna, additional, Cross, Kathryn, additional, Kok, Khoon‐S., additional, Wegmann, Udo, additional, Gil‐Cardoso, Katherine, additional, Bentley, Eleanor G., additional, Al Katy, Sanaria H.M., additional, Coombes, Janine L., additional, Kipar, Anja, additional, Stentz, Regis, additional, Stewart, James P., additional, and Carding, Simon R., additional

Published
2019
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35. Use of Bacteroides-derived microvesicles for mucosal vaccines

Author

Miquel-Clopes, Ariadna, primary, Carvalho, Ana L., additional, Wegmann, Udo, additional, Bentley, Eleanor G., additional, Al-Katy, Sanaria H.M., additional, Coombes, Janine L., additional, Kipar, Anja, additional, Stentz, Regis, additional, Stewart, James P., additional, and Carding, Simon R., additional

Published
2019
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36. Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract

Author

Carvalho, Ana L, Fonseca, Sonia, Miquel-Clopés, Ariadna, Cross, Kathryn, Kok, Khoon-S, Wegmann, Udo, Gil-Cardoso, Katherine, Bentley, Eleanor G, Al Katy, Sanaria H M, Coombes, Janine L, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, Stentz, Regis, Stewart, James P, Carding, Simon R, Carvalho, Ana L, Fonseca, Sonia, Miquel-Clopés, Ariadna, Cross, Kathryn, Kok, Khoon-S, Wegmann, Udo, Gil-Cardoso, Katherine, Bentley, Eleanor G, Al Katy, Sanaria H M, Coombes, Janine L, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, Stentz, Regis, Stewart, James P, and Carding, Simon R

Abstract

Gram-negative bacteria naturally produce and secrete nanosized outer membrane vesicles (OMVs). In the human gastrointestinal tract, OMVs produced by commensal Gram-negative bacteria can mediate interactions amongst host cells (including between epithelial cells and immune cells) and maintain microbial homeostasis. This OMV-mediated pathway for host-microbe interactions could be exploited to deliver biologically active proteins to the body. To test this we engineered the Gram-negative bacterium Bacteroides thetaiotaomicron (Bt), a prominent member of the intestinal microbiota of all animals, to incorporate bacteria-, virus- and human-derived proteins into its OMVs. We then used the engineered Bt OMVs to deliver these proteins to the respiratory and gastrointestinal (GI)-tract to protect against infection, tissue inflammation and injury. Our findings demonstrate the ability to express and package both Salmonella enterica ser. Typhimurium-derived vaccine antigens and influenza A virus (IAV)-derived vaccine antigens within or on the outer membrane of Bt OMVs. These antigens were in a form capable of eliciting antigen-specific immune and antibody responses in both mucosal tissues and systemically. Furthermore, immunisation with OMVs containing the core stalk region of the IAV H5 hemagglutinin from an H5N1 strain induced heterotypic protection in mice to a 10-fold lethal dose of an unrelated subtype (H1N1) of IAV. We also showed that OMVs could express the human therapeutic protein, keratinocyte growth factor-2 (KGF-2), in a stable form that, when delivered orally, reduced disease severity and promoted intestinal epithelial repair and recovery in animals administered colitis-inducing dextran sodium sulfate. Collectively, our data demonstrates the utility and effectiveness of using Bt OMVs as a mucosal biologics and drug delivery platform technology.

Published
2019

37. Promising biomolecules

Author

Oliveira, Isabel M., Carvalho, Ana L., Radhouani, Hajer, Gonçalves, Cristiana, Oliveira, J. M., Reis, R. L., and Universidade do Minho

Subjects
Cartilage repair, Osteochondral defects, Bone repair, Natural biomolecules, Synthetic biomolecules
Abstract

The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given., (undefined), info:eu-repo/semantics/publishedVersion

Published
2018

38. BRUGADA SYNDROME: A 9 YEAR RETROSPECTIVE ANALYSIS

Author

Lopes-de-Almeida, Maria, Sá, Joaquim de, Carminho, Teresa, Rosmaninho-Salgado, Joana, Carvalho, Ana L, Louro, Pedro, Garabal, Ana, Reis, Cláudia F, Oliveira, Renata, Maia, Sofia, Ramos, Fabiana, Sousa, Sérgio B, Venâncio, Margarida, Ramos, Lina, and Saraiva, Jorge M

Subjects
lcsh:RJ1-570, lcsh:Pediatrics, lcsh:Gynecology and obstetrics, lcsh:RG1-991
Abstract

NASCER E CRESCER - BIRTH AND GROWTH MEDICAL JOURNAL, Vol 25 (2016): Supplement I: XLV Conferências de Genética Doutor Jacinto Magalhães

Published
2016

42. Heterodimeric nitrate reductase (NapAB) from Cupriavidus necator H16: purification, crystallization and preliminary X-ray analysis

Author

Coelho, Catarina, J. Gonzaléz, Pablo, Trincão, José, Carvalho, Ana L., Najmudin, Shabir, Moura, José J. G., Hettman, Thomas, Dieckman, Stephan, Moura, Isabel, and Romão, Maria J.

Abstract

Acta Cryst. (2007). F63, 516–519 The periplasmic nitrate reductase from Cupriavidus necator (also known as Ralstonia eutropha) is a heterodimer that is able to reduce nitrate to nitrite. It comprises a 91 kDa catalytic subunit (NapA) and a 17 kDa subunit (NapB) that is involved in electron transfer. The larger subunit contains a molybdenum active site with a bis-molybdopterin guanine dinucleotide cofactor as well as one [4Fe–4S] cluster, while the small subunit is a di-haem c-type cytochrome. Crystals of the oxidized form of this enzyme were obtained using polyethylene glycol 3350 as precipitant. A single crystal grown at the High Throughput Crystallization Laboratory of the EMBL in Grenoble diffracted to beyond 1.5 A ° at the ESRF (ID14-1), which is the highest resolution reported to date for a nitrate reductase. The unit-cell parameters are a = 142.2, b = 82.4, c = 96.8 A ° , ß = 100.7°, space group C2, and one heterodimer is present per asymmetric unit.

Published
2007

43. crystallization and structure determination using soft X-rays

Author

Moura, Isabel, Santos-Silva, Teresa, Trincão, José, Carvalho, Ana L., Auchère, Françoise, Moura, José J. G., and Romão, Maria J.

Abstract

Superoxide reductase is a 14 kDa metalloprotein containing a catalytic nonhaem iron centre [Fe(His)4Cys]. It is involved in defence mechanisms against oxygen toxicity, scavenging superoxide radicals from the cell. The oxidized form of Treponema pallidum superoxide reductase was crystallized in the presence of polyethylene glycol and magnesium chloride. Two crystal forms were obtained depending on the oxidizing agents used after purification: crystals grown in the presence of K3Fe(CN)6 belonged to space group P21 (unit-cell parameters a = 60.3, b = 59.9, c = 64.8 A ° , = 106.9 ) and diffracted beyond 1.60 A ° resolution, while crystals grown in the presence of Na2IrCl6 belonged to space group C2 (a = 119.4, b = 60.1, c = 65.6 A ° , = 104.9 ) and diffracted beyond 1.55 A ° . A highly redundant X-ray diffraction data set from the C2 crystal form collected on a copper rotating-anode generator ( = 1.542 A ° ) clearly defined the positions of the four Fe atoms present in the asymmetric unit by SAD methods. A MAD experiment at the iron absorption edge confirmed the positions of the previously determined iron sites and provided better phases for model building and refinement. Molecular replacement using the P21 data set was successful using a preliminary trace as a search model. A similar arrangement of the four protein molecules could be observed.

Published
2005

50. Pd 2 Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice.

Author

Vojtek, Martin, Gonçalves-Monteiro, Salomé, Šeminská, Patrícia, Valová, Katarína, Bellón, Loreto, Dias-Pereira, Patrícia, Marques, Franklim, Marques, Maria P. M., Batista de Carvalho, Ana L. M., Mota-Filipe, Helder, Ferreira, Isabel M. P. L. V. O., and Diniz, Carmen

Subjects
BREAST tumors, TRIPLE-negative breast cancer, SPERMINE, CHORIOALLANTOIS, BREAST implants, CANCER cell growth
Abstract

Pd2Spm 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 Pd2Spm 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. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd2Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd2Spm was observed in MDA-MB-231 cells (IC50 values of 7.3–8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5–228.9 µM). Pd2Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd2Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd2Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd2Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia. [ABSTRACT FROM AUTHOR]

Published
2022
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