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1.
Cancer Control ; 30: 10732748231175256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37148308

RESUMO

PURPOSE: Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. METHODS: In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians' request in the clinical care for therapy decisions. Kaplan-Meier survival curves were estimated to characterize the time-to-event variables. RESULTS: Patients median age was 61 years (range: 14-87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment (P = .7). CONCLUSION: CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.


Assuntos
Países em Desenvolvimento , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Mutação , Genômica , Sequenciamento de Nucleotídeos em Larga Escala
2.
Biomedica ; 42(4): 574-590, 2022 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36511679

RESUMO

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.


Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Bevacizumab , Sunitinibe , Everolimo , Estudos Retrospectivos , Neoplasias Meníngeas/genética
3.
Biomédica (Bogotá) ; 42(4): 574-590, oct.-dic. 2022. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1420307

RESUMO

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.


Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were the only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.


Assuntos
Meningioma , Telomerase , Mutação com Ganho de Função
4.
Transl Oncol ; 15(1): 101276, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34823093

RESUMO

BACKGROUND: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. METHODS: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. RESULTS: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27-9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1-16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7-8.2%) and Bolivar with 2.4% (95%CI 0-7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. CONCLUSIONS: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

5.
J Neurooncol ; 154(3): 353-364, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34498213

RESUMO

BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioblastoma , Acrilamidas , Adulto , Idoso , Compostos de Anilina , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB/genética , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , Estudos Retrospectivos
6.
Oncol Ther ; 9(1): 89-110, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33689160

RESUMO

Precision medicine has impacted the field of medical oncology by introducing personalized therapies, improving all measurable outcomes. This field, in turn, has expanded to obtaining and analyzing a vast and ever-increasing amount of genomic information. One technique currently applied is the liquid biopsy, which consists of detecting and isolating DNA and exosomes in cancer patients. Newly developed techniques have made it possible to use the liquid biopsy in a wide range of settings. However, challenges regarding the validation of its clinical utility exist because of a lack of standardization across different techniques and tumor types, confounder genomic information, lack of appropriate clinical trial designs, and a non-measured, and therefore not estimated, economic impact on population health. Nowadays, liquid biopsy is not routinely used, but ongoing research is increasing its popularity, and a new era in oncology is developing. Therefore, it is essential to have an in-depth understanding of the liquid biopsy technique. In this review, we summarize the leading techniques and liquid biopsy applications in cancer.

7.
Thorac Cancer ; 12(9): 1328-1335, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33729676

RESUMO

BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.


Assuntos
Timoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
JCO Precis Oncol ; 5: 839-848, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34994616

RESUMO

PURPOSE: BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-triggered apoptosis in EGFR-mutant non-small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS: A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS: Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION: EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Proteína 11 Semelhante a Bcl-2/genética , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Combinação de Medicamentos , Receptores ErbB/antagonistas & inibidores , Feminino , Deleção de Genes , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Polimorfismo Genético , Estudos Retrospectivos , Adulto Jovem
9.
Front Oncol ; 10: 588932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33384957

RESUMO

BACKGROUND: Lung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform. METHODS: The comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS). RESULTS: A total of 26 samples were included, median age was 67 years (r, 33-83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2-49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05). CONCLUSIONS: The genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.

10.
Front Oncol ; 9: 254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058075

RESUMO

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46-81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5-34.6] vs. 17.3 months [4.8-29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41-0.80), limited-stage disease (HR 0.56, 95% CI 0.40-0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60-0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

11.
Target Oncol ; 13(5): 621-629, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30284706

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp. PATIENTS AND METHODS: Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status. RESULTS: 30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3-34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7) vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043). CONCLUSION: Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Amplificação de Genes , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto Jovem
12.
Cult. cuid. enferm ; 15(1): 23-37, 2018.
Artigo em Espanhol | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-987668

RESUMO

Desde hace varios años, en diferentes países se viene manifestando la necesidad de retomar el parto como un proceso humanizado, para ello se habla de la desmedicalización parto simplemente vaginal, sino abordando aspectos de orden cultural y social. El parto es una experiencia única e importante para cada mujer, proceso que se espera como una experiencia positiva, percibiéndose de forma diferente en función del contexto cultural y social. En la medida en la que el personal de enfermería acompañe cada mujer en el proceso de parto y aborde creencias y prácticas culturales de acuerdo al contexto de la mujer por dar a luz, se propenderá por garantizar que la experiencia culmine de manera positiva


For several years, the need to resume delivery as a humanized process has been manifested but rather by addressing Aspects of cultural and social order. Childbirth is a unique and important experience that for each woman, it is expected as a positive experience given that in eachTo the extent that the development and accompaniment given by nurses to each woman in theprocess addresses beliefs and aspects of their social and cultural context, it will tend to guarantee that the experience culminates in a positive way


Assuntos
Humanos , Vulnerabilidade Sexual
13.
J Microbiol ; 51(4): 448-52, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23990295

RESUMO

Resistance of Helicobacter pylori to clarithromycin is the most common cause of treatment failure in patients with H. pylori infections. This study describes the MICs and the presence of 23S rRNA mutations of H. pylori isolates from Bogotá, D.C., Colombia. H. pylori were isolated from gastric biopsies from patients with functional dyspepsia. Clarithromycin susceptibility was investigated by agar dilution and strains were considered resistant if the MIC was ≥ 1 µg/ml. DNA sequences of the 23S rRNA gene of strains resistant and sensitive to clarithromycin were determined to identify specific point mutations. Clarithromycin resistance was present in 13.6% of patients by agar dilution. The A2143G, A2142G and A2142C mutations were found in 90.5, 7.1, and 2.4% of H. pylori strains with resistance genotype.The resistant phenotype was associated with 23S rRNA resistance genotype in 85.7% of isolates. The point mutations in 23S rRNA were well correlated with MICs values for clarithromycin.


Assuntos
Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Genótipo , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Testes de Sensibilidade Microbiana , Fenótipo , Adulto , Idoso , Antibacterianos/farmacologia , Colômbia , Análise Mutacional de DNA , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Mutação , RNA Ribossômico 23S/genética , Adulto Jovem
14.
Biomédica (Bogotá) ; 32(3): 375-385, jul.-set. 2012. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: lil-663718

RESUMO

Introducción. Las enfermedades transmitidas por alimentos son un serio problema de salud pública y, el pollo, uno de los alimentos asociados con ellas. Objetivo. Determinar la distribución y frecuencia de brotes alimentarios asociados al consumo de pollo contaminado por Salmonella spp., Listeria monocytogenes y Staphylococus aureus, mediante una revisión sistemática de la literatura científica. Materiales y métodos. Se buscaron los estudios de brotes asociados a Salmonella spp., S. aureus y L. monocytogenes, en las bases de datos Medline, Pubmed, Science Direct,SciELO,Librería Cochrane (CCRT),Biblioteca Virtual en Salud (BVS), Highwire,HINARI y MedicLatina. Se obtuvieron los datos para el cálculo de odds ratios (OR) mediante la elaboración de tablas de contingencia en el programa RevMan5™. Resultados. Siete artículos cumplieron con los criterios de inclusión y no se encontraron reportes de L. monocytogenes. El OR global fue de 3,01 (IC95% 2,37-3,81), lo que se interpreta como una asociación significativa entre el consumo de pollo contaminado y la infección alimentaria. Se presentó heterogeneidad en los estudios incluidos (p=0,03), por lo que fue necesario un análisis por subgrupos de microorganismos; para el caso de Salmonella spp., el OR fue de 2,67 (IC95% 2,09-3,41). No se hizo análisis para S. aureus por reportarse un solo artículo. Conclusiones. Se encontró un OR de 2,61, lo que indica que hay una fuerte asociación entre el consumo de pollo y la adquisición de salmonelosis. El principal factor de riesgo para adquirir salmonelosis es el consumo de pollo de asadero en los restaurantes.


Introduction. Food borne diseases are a serious public health problem. Poultry are often associated with these outbreaks. Objective. A systematic review of the literature is provided concerning the distribution and frequency of food borne outbreaks associated with consumption of chicken contaminated with Salmonella spp., Listeria monocytogenes and Staphylococcus aureus. Materials and methods. The search for studies of outbreaks associated with Salmonella, S. aureus and L. monocytogenes was conducted in Medline, Pubmed, Science Direct, Scielo, Cochrane Library (CCRT), Virtual Health Library (VHL), Highwire, HINARI and MedicLatina. Data were obtained for the calculation of odds ratio (OR) by preparing contingency tables using the RevMan5 program. Results. Seven articles met the inclusion criteria; however, no reports of L. monocytogenes were obtained. The overall OR was 3.01 (95% CI: 2.37, 3.81); this was interpreted as a significant association between the consumption of contaminated chicken and food poisoning. In the included studies heterogeneity (p= 0.03) was presented, so it took a subgroup analysis of microorganisms, in the case of Salmonella OR was 2.67 (95% CI: 2.09 -3.41). No analysis was made for S. aureus reported a single article. Conclusions. The OR indicated a strong association between chicken consumption and acquisition of salmonellosis. The main risk factor for acquiring salmonellosis is the consumption of chicken from grill restaurants.


Assuntos
Animais , Humanos , Galinhas/microbiologia , Surtos de Doenças , Contaminação de Alimentos , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Listeria monocytogenes/isolamento & purificação , Carne/efeitos adversos , Salmonella/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , África/epidemiologia , América/epidemiologia , Estudos de Casos e Controles , Culinária , Europa (Continente)/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Razão de Chances , Viés de Publicação , Restaurantes , Fatores de Risco , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/etiologia , Intoxicação Alimentar por Salmonella/microbiologia , Intoxicação Alimentar Estafilocócica/epidemiologia , Intoxicação Alimentar Estafilocócica/etiologia , Intoxicação Alimentar Estafilocócica/microbiologia
15.
Biomedica ; 32(3): 375-85, 2012 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-23715186

RESUMO

INTRODUCTION: Food borne diseases are a serious public health problem. Poultry are often associated with these outbreaks. OBJECTIVE: A systematic review of the literature is provided concerning the distribution and frequency of food borne outbreaks associated with consumption of chicken contaminated with Salmonella spp., Listeria monocytogenes and Staphylococcus aureus. MATERIALS AND METHODS: The search for studies of outbreaks associated with Salmonella, S. aureus and L. monocytogenes was conducted in Medline, PubMed, Science Direct, Scielo, Cochrane Library (CCRT), Virtual Health Library (VHL), Highwire, HINARI and MedicLatina. Data were obtained for the calculation of odds ratio (OR) by preparing contingency tables using the RevMan5 program. RESULTS: Seven articles met the inclusion criteria; however, no reports of L. monocytogenes were obtained. The overall OR was 3.01 (95% CI: 2.37, 3.81); this was interpreted as a significant association between the consumption of contaminated chicken and food poisoning. In the included studies heterogeneity (p= 0.03) was presented, so it took a subgroup analysis of microorganisms, in the case of Salmonella OR was 2.67 (95% CI: 2.09 -3.41). No analysis was made for S. aureus reported a single article. CONCLUSIONS: The OR indicated a strong association between chicken consumption and acquisition of salmonellosis. The main risk factor for acquiring salmonellosis is the consumption of chicken from grill restaurants.


Assuntos
Galinhas/microbiologia , Surtos de Doenças , Contaminação de Alimentos , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Listeria monocytogenes/isolamento & purificação , Carne/efeitos adversos , Salmonella/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , África/epidemiologia , América/epidemiologia , Animais , Estudos de Casos e Controles , Culinária , Europa (Continente)/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Razão de Chances , Viés de Publicação , Restaurantes , Fatores de Risco , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/etiologia , Intoxicação Alimentar por Salmonella/microbiologia , Intoxicação Alimentar Estafilocócica/epidemiologia , Intoxicação Alimentar Estafilocócica/etiologia , Intoxicação Alimentar Estafilocócica/microbiologia
16.
Biomed Pharmacother ; 2010 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-21067888

RESUMO

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.bionut.2010.09.005. The duplicate article has therefore been withdrawn.

17.
Int J Food Sci Nutr ; 60 Suppl 7: 278-88, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19657848

RESUMO

Golden-yellow and purple-red tamarillos (Solanum betaceum Cav.) cultivated in Ecuador were studied for their physical properties, proximate composition, pH, degrees Brix, acidity, sugars, organic acids, minerals, vitamin C and beta-carotene content in the edible part. Results were compared with those for Spanish fruits. The golden-yellow and purple-red Ecuadorian fruits were larger (107 and 188 g) than the respective Spanish fruits (43 and 63 g), softer but generally similar in chemical composition except for fat (0.72 and 0.6%) and malic acid (0.32 and 0.53%) contents in the golden-yellow and purple-red Ecuadorian fruits. Tamarillo fruits are a good source of potassium (approximately 400 mg/100 g fresh weight). Total phenolics in the golden-yellow and purple-red varieties were 125 and 187 mg gallic acid equivalents/100 g fresh weight, respectively. The golden-yellow variety had weaker anti-DPPH radical activity than the purple-red variety. Flavonols were only found in the peel of both varieties, while hydroxycinnamic acid derivatives were found in peel and pulp.


Assuntos
Fenômenos Químicos , Frutas/química , Pigmentação , Solanum/química , Ácido Ascórbico/análise , Cálcio da Dieta/análise , Ácidos Carboxílicos/análise , Ácidos Cumáricos/análise , Carboidratos da Dieta/análise , Equador , Flavonóis/análise , Sequestradores de Radicais Livres/análise , Frutas/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Tamanho do Órgão , Especificidade de Órgãos , Fenóis/análise , Potássio na Dieta/análise , Especificidade da Espécie , Oligoelementos/análise , beta Caroteno/análise
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