Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60- month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸ 1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.Fil: de Almeida, Liz María. Instituto Nacional de Câncer; BrasilFil: Cortés, Sandra. Pontificia Universidad Católica de Chile; ChileFil: Vilensky, Marta. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Cortes Sanabria, Laura. Hospital de Especialidades Centro Medico Nacional Siglo XXI; MéxicoFil: de Souza, Mirian. Instituto Nacional de Câncer; BrasilFil: Barbeito, Rafael Alonso. Universidad de la República; UruguayFil: Abdelhay, Eliana. Instituto Nacional de Câncer; BrasilFil: Artagaveytia, Nora. Universidad de la Republica; UruguayFil: Daneri Navarro, Adrian. Universidad de Guadalajara; MéxicoFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa. Hospital Maria Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Bravo, Alicia I.. Hospital Higa Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la República; UruguayFil: Carraro, Dirce Maria. A. C. Camargo Cancer Center; BrasilFil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Instituto Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. Instituto Nacional de Câncer; BrasilFil: Silva-Garcia, Aida A.. Universidad de Guadalajara; MéxicoFil: Viña, Stella. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Zagame, Livia. Instituto Jalisciense de Cancerología; MéxicoFil: Jones, Beth. University of Yale; Estados UnidosFil: Szklo, Moysés. University Johns Hopkins; Estados Unido

The Depletion of Nuclear Glutathione Impairs Cell Proliferation in 3t3 Fibroblasts

BACKGROUND:Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate. PRINCIPAL FINDINGS:We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM) and buthionine sulfoximine (BSO), and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation. CONCLUSIONS:Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle

The Human Milk Metabolome Reveals Diverse Oligosaccharide Profiles

Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (<20%), including lactose, urea, glutamate, myo-inositol, and creatinine. Principal components analysis identified 2 clear groups of participants who were differentiable on the basis of milk oligosaccharide concentration and who were classified as secretors or nonsecretors of fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'-fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of the interrelations between the milk sugars by using Spearman rank correlations revealed significant positive and negative associations, including positive correlations between fucose and products of the FUT2 gene and negative correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene. The total concentration of milk oligosaccharides was conserved among participants (%CV = 18%), suggesting tight regulation of total oligosaccharide production; however, concentrations of specific oligosaccharides varied widely between participants (%CV = 30.4-84.3%). The variability in certain milk metabolites suggests possible roles in infant or infant gut microbial development. This trial was registered at clinicaltrials.gov as NCT01817127

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity. Copyright © 2022 de Almeida, Cortés, Vilensky, Valenzuela, Cortes-Sanabria, de Souza, Barbeito, Abdelhay, Artagaveytia, Daneri-Navarro, Llera, Müller, Podhajcer, Velazquez, Alcoba, Alonso, Bravo, Camejo, Carraro, Castro, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cristerna, Delgado, Breitenbach, Fernández, Fernández, Fernández, Franco-Topete, Gaete, Gómez, Gonzalez-Ramirez, Guerrero, Gutierrez-Rubio, Jalfin, Lopez-Vazquez, Loria, Míguez, Moran-Mendoza, Morgan-Villela, Mussetti, Nagai, Oceguera-Villanueva, Reis, Retamales, Rodriguez, Rosales, Salas-Gonzalez, Segovia, Sendoya, Silva-Garcia, Viña, Zagame, Jones, Szklo and United States-Latin American Cancer Research Network (US-LACRN).Fil: de Almeida, Liz Maria. Instituto Nacional de Cáncer; BrasilFil: Cortés, Sandra. Pontificia Universidad Católica de Chile; ChileFil: Vilensky, Marta. Instituto de Oncología Angel Roffo; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Cortes-Sanabria, Laura. Hospital de Especialidades, CMNO-IMSS; MéxicoFil: de Souza, Mirian. Instituto Nacional de Cáncer; BrasilFil: Barbeito, Rafael Alonso. Facultad de Medicina; ArgentinaFil: Abdelhay, Eliana. Instituto Nacional de Cáncer; BrasilFil: Artagaveytia, Nora. Hospital de Clínicas Manuel Quintela. Universidad de la República; UruguayFil: Daneri-Navarro, Adrian. Universidad de Guadalajara; MéxicoFil: Llera, Andrea S. CONICET. Fundación Instituto Leloir; ArgentinaFil: Müller, Bettina. Instituto Nacional del Cáncer; ArgentinaFil: Podhajcer, Osvaldo L. CONICET. Fundación Instituto Leloir; ArgentinaFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa. Hospital Municipal de Oncología María Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; ArgentinaFil: Bravo, Alicia I. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Hospital de Clínicas Manuel Quintela. Universidad de la República; UruguayFil: Carraro, Dirce Maria. AC Camargo Cancer Center; BrasilFil: Castro, Mónica. Instituto de Oncología Angel Roffo; ArgentinaFil: Cataldi, Sandra. Instituto Nacional de Cáncer; UruguayFil: Cayota, Alfonso. Institut Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. Instituto Nacional de Cáncer; BrasilFil: Del Toro-Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo-Cristerna, Raul. Hospital de Especialidades. CMNO-IMSS; MéxicoFil: Delgado, Lucia. Hospital de Clínicas Manuel Quintela; UruguayFil: Breitenbach, Marisa Dreyer. Universidade do Estado do Rio de Janeiro; BrasilFil: Fernández, Elmer. Universidad Católica de Córdoba. CONICET. Centro de Investigaciones en Bioquímica Clínica e Inmunologia; ArgentinaFil: Fernández, Jorge. Instituto de Salud Pública; ChileFil: Fernández, Wanda. Hospital San Borja Arriarán; ChileFil: Franco-Topete, Ramon A. OPD Hospital Civil de Guadalajara. Universidad de Guadalajara; MéxicoFil: Gaete, Fancy. Hospital Luis Tisne; ChileFil: Gómez, Jorge. Texas A&M University; Estados UnidosFil: Gonzalez-Ramirez, Leivy P. Universidad de Guadalajara; MéxicoFil: Guerrero, Marisol. Hospital San José; ChileFil: Gutierrez-Rubio, Susan A. Universidad de Guadalajara; MéxicoFil: Jalfin, Beatriz. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Lopez-Vazquez, Alejandra. Universidad de Sonora; MéxicoFil: Loria, Dora. Instituto de Oncología Angel Roffo; ArgentinaFil: Míguez, Silvia. Hospital Municipal de Oncología María Curie; ArgentinaFil: Moran-Mendoza, Andres de J. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Morgan-Villela, Gilberto. Hospital de Especialidades. CMNO-IMSS; MéxicoFil: Mussetti, Carina. Registro Nacional de Cancer; UruguayFil: Nagai, Maria Aparecida. Instituto de Câncer de São Paulo; BrasilFil: Oceguera-Villanueva, Antonio. Instituto Jalisciense de Cancerologia; MéxicoFil: Reis, Rui M. Hospital de Câncer de Barretos; BrasilFil: Retamales, Javier. Grupo Oncológico Cooperativo Chileno de Investigación; ChileFil: Rodriguez, Robinson. Hospital Central de las Fuerzas Armadas; UruguayFil: Rosales, Cristina, Hospital Municipal de Oncología María Curie; ArgentinaFil: Salas-Gonzalez, Efrain. Hospital San José; ChileFil: Segovia, Laura. Hospital Barros Luco Trudeau; ChileFil: Sendoya, Juan M. CONICET. Fundación Instituto Leloir,; ArgentinaFil: Silva-Garcia, Aida A. OPD Hospital Civil de Guadalajara. Universidad de Guadalajara; MéxicoFil: Viña, Stella. Instituto de Oncología Angel Roffo; ArgentinaFil: Zagame, Livia. Instituto Jalisciense de Cancerologia; MéxicoFil: Jones, Beth. Yale University. Yale School of Public Health; Estados UnidosFil: Szklo, Moysés. Johns Hopkins University. Johns Hopkins Bloomberg School of Public Health; Estados Unido