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1.
BMC Cancer ; 19(1): 169, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30795751

RESUMO

BACKGROUND: Liver metastases of breast cancer are frequent and can recur even after "complete/R0" resection in combination with systemic and hormonal treatments. The aim of this study was to analyze throughout repeat hepatectomies for liver metastases the evolution of PI3KCA gene mutational status. METHODS: All liver metastases nodules (n = 70) from 19 women who underwent at least 2 liver resections were reexamined. DNA extraction from archived tumoral tissue was performed and the major 'hot spot' mutations in the helical and catalytic domains of PI3KCA have been analyzed using Massarray platform (Agena Bioscience) based on allelic discrimination PCR amplification followed by sensitive mass spectrometry detection. RESULTS: The two major somatic hot spot PI3KCA mutations were found in 27 (38.6%) nodules corresponding to 8 of the 19 patients (42%). The frequency of women whose breast cancer liver metastases (BCLM) carries PI3KCA mutations increased from the first to the third hepatectomy. Tumors carrying PI3KCA mutations are significantly larger and more frequently observed when resections were R0 compared to patients with no PI3KCA mutation. CONCLUSION: PI3KCA mutations are frequently observed in BCLM and persist along with the recurrence. Their identification in circulating tumor cells should become a useful biomarker in the routine practice of breast cancer management to prevent tumor recurrence and overcome the problems of intra- and inter-tumoral heterogeneity of the current biomarkers.


Assuntos
Neoplasias da Mama/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Mutação/genética , Proteínas Nucleares/genética , Reoperação/estatística & dados numéricos , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , França/epidemiologia , Humanos , Fígado/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Prevalência , Recidiva , Fatores de Tempo
2.
J Chem Inf Model ; 52(12): 3341-51, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23094651

RESUMO

Anuran skin is known to be a rich source of antimicrobial peptides although their therapeutic potential is often limited due to their toxicity against mammalian cells. The analysis of structure-activity relationships among anuran antimicrobial peptides provided the parameters to construct the "Mutator" tool for improving their selectivity for bacterial cells, by suggesting appropriate point substitutions. Double substitution analogues [K2, K16] of the Xenopus tropicalis peptide XT-7 and [I2, K19] of the Ascaphus truei peptide ascaphin-8 were predicted by this tool to have an increased 'therapeutic index' (TI = HC(50)/MIC for erythrocytes with respect to bacteria) > 80. The mutated peptides were synthesized and respectively found to have experimental TI values > 130 for S. aureus or E. coli, a considerable improvement with respect to TI < 37 for the parent compounds. Circular dichroism studies of the mutated peptides suggested this may in part be due to variations in the α-helical structure. For P. aeruginosa, which is more resistant to XT-7, the TI increased in the mutated peptide from 5 to >270, also due to a significant improvement in minimal inhibitory concentration. We have shown that the Mutator tool is capable of suggesting limited variations in natural anuran peptides capable of increasing peptide selectivity, by decreasing toxicity against mammalian erythrocytes, in general without compromising antibacterial activity. The tool is freely available on the Mutator Web server at http://split4.pmfst.hr/mutator/.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/toxicidade , Anuros , Descoberta de Drogas/métodos , Pele/química , Animais , Peptídeos Catiônicos Antimicrobianos/química , Bactérias/efeitos dos fármacos , Dicroísmo Circular , Hemólise/efeitos dos fármacos , Internet , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Oligopeptídeos/toxicidade , Estrutura Secundária de Proteína , Software , Relação Estrutura-Atividade , Proteínas de Xenopus/química , Proteínas de Xenopus/farmacologia , Proteínas de Xenopus/toxicidade
3.
Zootaxa ; 4951(2): zootaxa.4951.2.11, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33903410

RESUMO

The land flatworm Platydemus manokwari (Platyhelminthes, Geoplanidae) is recorded from the islands of Guadeloupe, Martinique, and Saint Martin in the Caribbean arc. Photographs and records were obtained mainly from citizen science and ranged from the end of 2018 to February 2021; several specimens were deposited in the collections of the Muséum National d'Histoire Naturelle in Paris, France. Thirty records were from Guadeloupe, but only one from Martinique and from Saint Martin, respectively. The COI sequences of 3 specimens from Guadeloupe show that they belong to the World haplotype also found in many countries. We also report P. manokwari from Fort Myers, Florida, USA, with molecular characterization, which was also the World haplotype. This is the first published record of P. manokwari for Guadeloupe, Martinique and Saint Martin and the second for islands in the Caribbean, after Puerto Rico.


Assuntos
Platelmintos , Animais , Guadalupe , Martinica , Platelmintos/classificação , Índias Ocidentais
4.
J Thorac Oncol ; 13(12): 1962-1967, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30149144

RESUMO

INTRODUCTION: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. METHODS: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. RESULTS: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. CONCLUSION: IHC is not a relevant screening tool for MET abnormalities in LSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Éxons/genética , Amplificação de Genes , Neoplasias Pulmonares/diagnóstico , Mutação , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Gigantes/diagnóstico , Carcinoma de Células Gigantes/genética , Carcinoma de Células Gigantes/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/metabolismo
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