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1.
Rev Med Chil ; 151(3): 381-386, 2023 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-38293884

RESUMO

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Células T , Masculino , Humanos , Adulto , Testículo/patologia , Herpesvirus Humano 4 , Metotrexato , Linfoma de Células T/patologia , Linfoma de Células T/terapia
2.
Rev Invest Clin ; 75(5): 259-271, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37918013

RESUMO

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.


Assuntos
Carcinoma , Neoplasias do Colo , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Carcinoma/patologia , Estadiamento de Neoplasias
3.
Ann Surg Oncol ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35320428

RESUMO

BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

4.
BMC Cancer ; 21(1): 892, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353292

RESUMO

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12-18 months as median survival, and 5-10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary. METHODS: Immunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250 mg/m2) in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks as first-line therapy. RESULTS: From the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 (± 219, 019.8); 104,647.1 (± 65, 773.4); 4536.5 (± 5, 521.3); and 2458.7 (± 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8 months, p = < 0.001). Furthermore, high expression of RRM1 and ERCC1 were associated with an increased median OS compared with their lower expression counterparts; [(23.1 vs 7.2 months for RRM1 p = < 0.001) and (17.4 vs 9.8 months for ERCC1 p = 0.018)]. CONCLUSIONS: ERCC1 and RRM1 are useful biomarkers that predict better survival outcomes in patients with advanced MPM treated with continuous infusion of gemcitabine plus cisplatin.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/metabolismo , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Cisplatino/administração & dosagem , Proteínas de Ligação a DNA/genética , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Endonucleases/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Prognóstico , Ribonucleosídeo Difosfato Redutase/genética , Gencitabina
5.
Gynecol Obstet Invest ; 86(3): 293-298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111875

RESUMO

OBJECTIVE: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). DESIGN: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. METHODS: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher's exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. RESULTS: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). LIMITATIONS: Our main limitation was a reduced sample size. CONCLUSION: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.


Assuntos
Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas Cervicais , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Biomarcadores Tumorais , Estudos de Casos e Controles , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Antígeno Ki-67 , Recidiva Local de Neoplasia
6.
Rev Med Chil ; 149(8): 1231-1235, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35319711

RESUMO

Primary myocardial involvement of Diffuse Large B-Cell lymphoma is extremely rare, accounting for 0.5 % of all lymphomas. We report a 65-year-old male, presenting with an acute cardiac tamponade, which was drained. A pericardial window with myocardial biopsy was carried out, disclosing a diffuse large B cell lymphoma. He received 6 cycles of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), without response. Finally, a palliative chemotherapy with gemcitabine plus oxaliplatin was prescribed.


Assuntos
Linfoma Difuso de Grandes Células B , Idoso , Ciclofosfamida/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
7.
Rev Invest Clin ; 73(6): 362-370, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34044429

RESUMO

BACKGROUND: Novel prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) are required in the era of Rituximab. OBJECTIVE: The objective of the study was to study the prognostic impact of exon-16 enhancer-of-zeste homolog-2 (EZH2) mutations in patients with DLBCL. METHODS: In a cohort of patients with DLBCL treated between 2015 and 2017, we analyzed the presence of EZH2 mutations and their association with clinical response (CR), relapse, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 198 patients were included; of them, 30 (15.2%) had mutations at codon 641, in exon 16 of EZH2. Response was achieved in 151 patients (76.3%), and 43 (21.7%) relapsed or progressed during follow-up. EZH2 mutations were associated with relapse/progression (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.98-1.42; p = 0.031), while a trend for not achieving a complete response was observed (RR: 0.876; 95%CI 0.74-1.038; p = 0.071). Of note, Tyr641His and Tyr641Ser EZH2 mutations were associated with shorter PFS (hazard ratio 3.234; 95% CI 1.149-9.1; p = 0.026). CONCLUSION: The presence of EZH2 mutations was negatively associated with relapse/progression and showed a trend for lack of complete response. Further studies are needed to define better the prognostic significance of these mutations in Mexican-Mestizo DLBCL patients.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos de Coortes , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Éxons , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Mutação , Prognóstico , Rituximab
8.
Oncology (Williston Park) ; 34(1): 21-27, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32645202

RESUMO

A 40-year-old woman presented with a productive cough and shortness of breath that limited her regular activities. Her past medical history was relevant for hypertension since 2016; it is well controlled and treated with enalapril 5 mg twice daily. She also revealed a past wood smoke exposure of 2 hours per day for 10 years during her childhood. A chest computed tomography (CT) scan was performed which showed a 30-mm lung nodule in the lower left lobe and mediastinal and ipsilateral pleural thickening with moderate pleural effusion and several bilateral lung metastases.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mutação , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
9.
Oncology ; 96(4): 207-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30476928

RESUMO

OBJECTIVE: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America. METHODS: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed. RESULTS: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%). CONCLUSIONS: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/genética , Rearranjo Gênico , Adenocarcinoma de Pulmão/diagnóstico , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Incidência , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Salud Publica Mex ; 61(3): 308-317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276344

RESUMO

OBJECTIVE: Targeted next-generation sequencing (t-NGS) has revolutionized clinical diagnosis allowing multiplexed detection of genomic alterations. This study evaluated the profile of somatic mutations by t-NGS in Mexican patients with nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Genomic DNA was extracted from 90 lung adenocarcinomas and sequences were generated for a panel of 48 cancer genes. Epidermal Growth Factor Receptor (EGFR) mutations were detected in parallel by quantitative PCR. RESULTS: The mutational profile of NSCLC revealed alterations in 27 genes, where TP53 (47.8%) and EGFR (36.7%) exhibited the highest mutation rates. EGFR Q787 mutations were present in 14 cases (15.6%), 10 cases had exon 19 deletions (11.1%), seven cases had L858R (7.8%). The mutational frequency for genes like EGFR, MET, HNF1A, HER2 and GUSB was different compared to caucasian population. CONCLUSIONS: t-NGS improved NSCLC treatments efficacy due to its sensitivity and specificity. A distinct pattern of somatic mutations was found in Mexican population.


OBJETIVO: La secuenciación dirigida de nueva generación (SNG) permite la detección múltiple de mutaciones. Este estudio evalúa el perfil de mutaciones somáticas por SNG en pacientes mexicanos con cáncer de pulmón de células no pequeñas(CPCNP). MATERIAL Y MÉTODOS: Se aisló ADN de 90 muestras de pacientes con CPCNP y se analizarón 48 genes relacionados con cáncer. Las mutaciones del receptor del factor de crecimiento epidérmico (EGFR) se detectaron por PCR cuantitativa. RESULTADOS: Se detectaron alteraciones en 27 genes. Las mutaciones más frecuentes fueron TP53 (47.8%) y EGFR (36.7%). En el gen EGFR, 14 casos fueron mutaciones Q787 (15.6%), 10 presentaron microdeleciones en el exón 19 (11.1%), y siete en L858R (7.8%). La frecuencia de mutación en EGFR, MET, HNF1A, HER2 y GUSB fue diferente en comparación con población caucásica. CONCLUSIONES: NGS modifica el tratamiento del paciente con CPCNP por su sensibilidad y especificidad para detectar mutaciones. La población mexicana presenta un perfil mutacional particula.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sequência de DNA
11.
Rev Invest Clin ; 71(5): 349-358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31599881

RESUMO

BACKGROUND: The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. OBJECTIVE: The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. RESULTS: From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. CONCLUSIONS: PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease.


Assuntos
Antineoplásicos/administração & dosagem , Imunoterapia/métodos , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Rev Med Chil ; 145(7): 945-949, 2017 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-29182205

RESUMO

We report a 73-year-old female patient with Castleman's disease coexistent with large B cell type non-Hodgkin's lymphoma in a right axillary lymphadenopathy. An excisional biopsy was performed: microscopically, the lymph node revealed the presence of numerous plasma cells and small lymphoid cells characteristic of Castleman's disease. An analysis of another portion of the specimen revealed lymphoid cells with large abnormal nuclei gathered locally that were CDD 79+, CD 38+ and MUM-1+ as well as positive for Kaposi sarcoma-associated herpesvirus and negative for Epstein Barr virus encoded RNA-1 (EBER).


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/complicações , Idoso , Hiperplasia do Linfonodo Gigante/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia
14.
Rev Med Chil ; 145(9): 1208-1212, 2017 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-29424411

RESUMO

Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination. Treatment with conventional chemotherapy is ineffective and allogeneic hematopoietic stem cell transplantation is required to achieve remission. We report three male patients, aged 23, 27 and 51 years with the disease. All had multiple, infiltrated pink plaques and nodules on the skin of their face, neck and thorax, measuring 1 to 12 cm in diameter. All tumors were histologically characterized by a monotonous proliferation of medium size cells with blastic features. Tumor cells were positive for CD123, CD56, CD4 and CD7 in all cases. After a mean of follow-up of 14.6 months, one patient died of the disease, one patient is alive and the disease relapsed after 17 months of remission and one patient is alive with no evidence of the disease.


Assuntos
Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Adulto , Biópsia , Medula Óssea/patologia , Evolução Fatal , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pele/patologia , Adulto Jovem
15.
Respir Res ; 17: 42, 2016 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-27098372

RESUMO

BACKGROUND: Tobacco-smoke is the major etiological factor related to lung cancer. However, other important factor is chronic wood smoke exposure (WSE). Approximately 30 % of lung cancer patients in Mexico have a history of WSE, and present different clinical, pathological and molecular characteristics compared to tobacco related lung cancer, including differences in mutational profiles. There are several molecular alterations identified in WSE associated lung cancer, however most studies have focused on the analysis of changes in several pathogenesis related proteins. METHODS: Our group evaluated gene expression profiles of primary lung adenocarcinoma, from patients with history of WSE or tobacco exposure. Differential expression between these two groups were studied through gene expression microarrays. RESULTS: Results of the gene expression profiling revealed 57 statistically significant genes (p < 0.01). The associated biological functional pathways included: lipid metabolism, biochemistry of small molecules, molecular transport, cell morphology, function and maintenance. A highlight of our analysis is that three of the main functional networks represent 37 differentially expressed genes out of the 57 found. These hubs are related with ubiquitin C, GABA(A) receptor-associated like protein; and the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: Our results reflect the intrinsic biology that sustains the development of adenocarcinoma related to WSE and show that there is a different gene expression profile of WSE associated lung adenocarcinoma compared to tobacco exposure, suggesting that they arise through different carcinogenic mechanisms, which may explain the clinical and mutation profile divergences between both lung adenocarcinomas.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Fuligem/intoxicação , Poluição por Fumaça de Tabaco/efeitos adversos , Madeira/efeitos adversos , Adenocarcinoma/etiologia , Exposição Ambiental , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/etiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Transcriptoma
16.
Int J Clin Oncol ; 21(6): 1051-1061, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27306217

RESUMO

BACKGROUND: Transcription factors such as retinoic acid receptor alpha (RARα) and beta (RARß) and Yin Yang 1 (YY1) are associated with the progression of non-small cell lung cancer (NSCLC). In particular, a lack of RARß expression is associated with NSCLC development. The aim of this study was to analyze the expression of RARα, RARß and YY1 and their relationship with prognosis in patients with advanced NSCLC. METHODS: The expression of RARα, RARß and YY1 was assessed by immunohistochemistry and quantitative computerized image software. RESULTS: Eighty-five patients treated with platinum-based chemotherapy were included in the analysis. The mean and standard deviation of the nuclear expression of RARα, RARß and YY1 were 184.5 ± 124.4, 18 ± 27 and 16.6 ± 20.5, respectively. The nuclear expression of RARß was associated with the nuclear expression of YY1 (R 2 = 0.28; p value < 0.0001). Patients with high nuclear expression of YY1 were likely to be non-smokers (61.9 vs 40.5 %). Median progression-free survival (PFS) was 5.9 months (3.48-8.28). Low expression of RARα was independently associated with worse PFS following chemotherapy (10.3 vs 5.46 months p = 0.040). Median overall survival (OS) was 15.6 months (4.5-26.7), and lower nuclear expression of RARß was independently associated with shorter OS (27.5 vs 8.7 months; p = 0.037). CONCLUSION: Our study suggests that the loss of RARs is associated with a worse prognosis and these receptors could be a potential molecular target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Cisplatino/uso terapêutico , Neoplasias Pulmonares , Receptores do Ácido Retinoico , Receptor alfa de Ácido Retinoico , Fator de Transcrição YY1 , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Diagnóstico por Computador , Intervalo Livre de Doença , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismo , Fatores de Transcrição , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
17.
BMC Cancer ; 15: 722, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26475474

RESUMO

BACKGROUND: The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. METHODS: Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed. RESULTS: Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38(-) and 34 % for p38(+) and for OS was 83 % for p38(-) and 47 % for p38(+). The p-p38(+) tissues expressed Bcl-2 and 90 % of p-p38(-) where Bcl-2(-). The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB. CONCLUSION: The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors.


Assuntos
Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Análise Serial de Tecidos , Vincristina/administração & dosagem , Proteínas Quinases p38 Ativadas por Mitógeno/genética
18.
Rev Invest Clin ; 66(5): 399-406, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25695382

RESUMO

The actual standard of care of diffuse large B-cell lymphoma (DLBCL) includes rituximab in combination with chemotherapy, with response rates up to 76%. However, this treatment may not be accessible to many patients, particularly in developing countries, where most of the treatment must be paid from the pocket of patients or their families. In México, since 2011 a federal program has fully covered this treatment of patients with DLBCL. At the Instituto Nacional de Cancerología (INCan) in Mexico City, 214 new cases with this disease were treated without cost with the standard of care in 20 months. The mean age at diagnosis was 56.7 ± 15.9 (22-91). This series of cases was compared with a retrospective analysis of cases with DLBCL attended at the INCan between 2006-2009. A total of 264 cases were retrospectively analyzed. No differences were found in demographic and clinical characteristics at time of diagnosis. However a clear positive impact was found in the group that received full treatment thanks to this new social coverage by this new social security program. The follow-up and completion of treatment was 99 %. In contrast; from 264 in the retrospective group (79%) were treated, but only 29 (10.9%) were able to receive an optimal treatment, including rituximab. These differences in treatments had a clearly impact on the response rate: 66.8 vs. 50.7% global response (full treatment vs. retrospective group, respectively). These results demonstrate the importance of social programs that may accessible standard treatment options in countries with limited resources.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Acessibilidade aos Serviços de Saúde/economia , Linfoma Difuso de Grandes Células B/patologia , Programas Nacionais de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/economia , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
Rev Med Chil ; 141(2): 260-3, 2013 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-23732501

RESUMO

Primary vascular tumors of lymph nodes are extremely rare with the exception of AlDS-related Kaposi's sarcoma. The diagnosis of epithelioid hemangio-endothelioma (EH) is difficult to make without ancillary studies, since it is devoid of morphological features indicating its vascular nature and it may be overlooked when it appears as a primary tumor of lymph nodes. Spindle and epithelioid hemangio-endothelioma (SEH) is considered to be a variant of EH, which has been reported to occur exclusively in lymph nodes and the spleen. We report a 70-year-old male with chronic lymphocytic leukemia (CLL) and left cervical lymphadenopathy. An excisional biopsy was performed, and microscopically the lymph node showed effacement of nodal architecture by a tumor composed of spindle cells disposed in intersecting fascicles, and characterized by abundant eosinophilic cytoplasm, elongated nuclei and conspicuous nucleoli. A second population of cells had an epithelioid appearance with intracyto-plasmic vacuoles containing red blood cells. lmmunohistochemically, the tumor cells were positive for CD31 and CD34. The final diagnosis was SEH of the lymph node.


Assuntos
Hemangioendotelioma/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfonodos/patologia , Idoso , Hemangioendotelioma/complicações , Humanos , Achados Incidentais , Leucemia Linfocítica Crônica de Células B/complicações , Masculino
20.
Rev Invest Clin ; 65 Suppl 2: s5-27, 2013 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-24459777

RESUMO

Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.


Assuntos
Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/terapia , Humanos , México
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