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1.
EMBO J ; 41(3): e108664, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34981847

RESUMO

Heat stress is a major environmental stress type that can limit plant growth and development. To survive sudden temperature increases, plants utilize the heat shock response, an ancient signaling pathway. Initial results had suggested a role for brassinosteroids (BRs) in this response. Brassinosteroids are growth-promoting steroid hormones whose activity is mediated by transcription factors of the BES1/BZR1 subfamily. Here, we provide evidence that BES1 can contribute to heat stress signaling. In response to heat, BES1 is activated even in the absence of BRs and directly binds to heat shock elements (HSEs), known binding sites of heat shock transcription factors (HSFs). HSFs of the HSFA1 type can interact with BES1 and facilitate its activity in HSE binding. These findings lead us to propose an extended model of the heat stress response in plants, in which the recruitment of BES1 is a means of heat stress signaling cross-talk with a central growth regulatory pathway.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Arabidopsis , Proteínas de Arabidopsis/genética , Brassinosteroides/metabolismo , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição de Choque Térmico/genética , Ativação Transcricional
2.
Lancet Oncol ; 24(1): 91-106, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436516

RESUMO

BACKGROUND: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing. METHODS: This genotype-first study used retrospective diagnostic and clinical data from 854 carriers of 398 rare CDH1 variants and 1021 relatives, irrespective of HDGC clinical criteria, from 29 institutions in ten member-countries of the European Reference Network on Tumour Risk Syndromes (ERN GENTURIS). Data were collected from Oct 1, 2018, to Sept 20, 2022. Variants were classified by molecular type and clinical actionability with the American College of Medical Genetics and Association for Molecular Pathology CDH1 guidelines (version 2). Families were categorised by whether they fulfilled the 2015 and 2020 HDGC clinical criteria. Genotype-phenotype associations were analysed by Student's t test, Kruskal-Wallis, χ2, and multivariable logistic regression models. Performance of HDGC clinical criteria sets were assessed with an equivalence test and Youden index, and the areas under the receiver operating characteristic curves were compared by Z test. FINDINGS: From 1971 phenotypes (contributed by 854 probands and 1021 relatives aged 1-93 years), 460 had gastric and breast cancer histology available. CDH1 truncating PV/LPVs occurred in 176 (21%) of 854 families and missense variants of unknown significance in 169 (20%) families. Multivariable logistic regression comparing phenotypes occurring in families carrying PV/LPVs or missense variants of unknown significance showed that lobular breast cancer had the greatest positive association with the presence of PV/LPVs (odds ratio 12·39 [95% CI 2·66-57·74], p=0·0014), followed by diffuse gastric cancer (8·00 [2·18-29·39], p=0·0017) and gastric cancer (7·81 [2·03-29·96], p=0·0027). 136 (77%) of 176 families carrying PV/LPVs fulfilled the 2015 HDGC criteria. Of the remaining 40 (23%) families, who did not fulfil the 2015 criteria, 11 fulfilled the 2020 HDGC criteria, and 18 had lobular breast cancer only or lobular breast cancer and gastric cancer, but did not meet the 2020 criteria. No specific CDH1 variant was found to predispose individuals specifically to lobular breast cancer, although 12 (7%) of 176 PV/LPV carrier families had lobular breast cancer only. Addition of three new lobular breast cancer-centred criteria improved testing sensitivity while retaining high specificity. The probability of finding CDH1 PV/LPVs in patients fulfilling the lobular breast cancer-expanded criteria, compared with the 2020 criteria, increased significantly (AUC 0·92 vs 0·88; Z score 3·54; p=0·0004). INTERPRETATION: CDH1 PV/LPVs were positively associated with HDGC-related phenotypes (lobular breast cancer, diffuse gastric cancer, and gastric cancer), and no evidence for a positive association with these phenotypes was found for CDH1 missense variants of unknown significance. CDH1 PV/LPVs occurred often in families with lobular breast cancer who did not fulfil the 2020 HDGC criteria, supporting the expansion of lobular breast cancer-centred criteria. FUNDING: European Reference Network on Genetic Tumour Risk Syndromes, European Regional Development Fund, Fundação para a Ciência e a Tecnologia (Portugal), Cancer Research UK, and European Union's Horizon 2020 research and innovation programme.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Neoplasias Gástricas , Feminino , Humanos , Antígenos CD/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/genética , Predisposição Genética para Doença , Genótipo , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Linhagem , Fenótipo , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Mutação de Sentido Incorreto
3.
Hered Cancer Clin Pract ; 21(1): 2, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709314

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear. CASE PRESENTATION: We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease. CONCLUSIONS: To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31413764

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) represent the most frequent mesenchymal tumor of the gastrointestinal tract. Less than 5% of them seem to be hereditary, being succinate dehydrogenase complex (SDHx) deficient disorders and neurofibromatosis type 1 the more related inherited conditions. Wild type (WT) KIT and PDGFRα GISTs constitute a clue for a hypothetical underlying germline condition. CASE PRESENTATION: We present a case of a 20 years old female diagnosed of a gastric WT GIST who developed hepatic metastases during her clinical course. No significant or typical phenotypic features suggestive of a specific syndrome were detected by physical examination. Also, her family history seemed to be irrelevant, since no other cases of GISTs, paragangliomas or pheochromocytomas were reported. Her paternal grandfather died as a consequence of a pituitary adenoma. In light of the age of tumor presentation and somatic features of gastric GIST, we performed genetic testing of SDHx genes. Analysis obtained from peripheral blood sample revealed the presence, in heterozygous state, of the c.1A > C; p.(Met1?) pathogenic variant in the SDHA. CONCLUSIONS: To the best of our knowledge, this is the first published report in which the c.1A > C; p.(Met1?) pathogenic variant in the SDHA is associated with a GIST. SDHA pathogenic variants increase the risk of paraganglioma, pheochromocytoma, GIST, pituitary adenoma and renal cancer in an autosomal dominant inherited condition named paraganglioma syndrome type 5. The absence of family history of tumors in SDHA pathogenic variants carriers could be related to its low penetrance. All patients diagnosed with WT GISTs should be referred to a hereditary cancer genetic counseling unit regardless of the age at presentation or the absence of a suspicious family history.

5.
Artigo em Inglês | MEDLINE | ID: mdl-28670351

RESUMO

Pancreatic cancer is a very aggressive disease with a poor prognosis. The majority of them are attributed to sporadic causes, especially to many modifiable risk factors such as tobacco or alcohol abuse. The principal histologic subtype of pancreatic cancer is ductal adenocarcinoma. Pancreatic neuroendocrine tumors, which constitute a more indolent entity, represent second type of pancreatic cancer in terms of incidence. Individuals with a family history of pancreatic cancer carry an increased risk of developing the disease, which may be related to an underlying hereditary component. Unfortunately, in the majority of these families the suspected germline genetic cause responsible of the disease will not be identified, but approximately in a 20% of the cases a hereditary cancer predisposition syndrome with increased risk of pancreatic cancer development can be recognized. This review will be focused on the leading hereditary cancer syndromes related to pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors. Additionally, we will try to explain clinical aspects related to the identification of germline mutations in pancreatic cancer patients and their potential implications in oncologic treatment decisions.

6.
BMC Cancer ; 15: 40, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25655792

RESUMO

BACKGROUND: The optimal form of exercise for individuals with cancer has yet to be identified, but there is evidence that exercise improves their quality of life. The aim of this study is to assess the efficacy and efficiency of an innovative physical exercise programme, for individuals undergoing chemotherapy for breast, gastrointestinal or non-small cell lung tumours, for improving quality of life, reducing level of fatigue, and enhancing functional capacity over time. DESIGN/METHODS: We will conduct a clinical trial in 66 patients with stage IV breast, gastrointestinal or non-small cell lung cancer, recruited by the Department of Oncology of the referral hospital from 4 primary care health centres of the Basque Health Service (Osakidetza). These patients will be randomised to one of two groups. The treatment common to both groups will be the usual care for cancer: optimized usual drug therapies and strengthening of self-care; in addition, patients in the intervention group will participate in a 2-month exercise programme, including both aerobic and strength exercises, supervised by nurses in their health centre. The principal outcome variable is health-related quality of life, measured blindly with the 30-item European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and Short Form-36 four times: at baseline, and 2, 6 and 12 months later. The secondary outcome variables are fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire), functional capacity (6-Minute Walk Test and cardiorespiratory test), muscle strength (hand-held dynamometry and sit-to-stand test), radiological response to treatment (Response Evaluation Criteria In Solid Tumors) and progression-free and overall survival. Age, sex, diagnosis, chemotherapy regimen, Eastern Cooperative Oncology Group performance status and smoking status will be considered as predictive variables. Data will be analysed on an intention-to-treat basis, comparing changes at each time point between groups, adjusting for baseline values by analysis of covariance. DISCUSSION: As well as achieving the objectives set, this study will provide us with information on patient perception of the care received and an opportunity to develop a project based on collaborative action between the primary care and oncology professionals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01786122 Registration date: 02/05/2013.


Assuntos
Protocolos Clínicos , Terapia por Exercício , Exercício Físico , Neoplasias/epidemiologia , Qualidade de Vida , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/terapia
7.
BMC Cancer ; 15: 495, 2015 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-26138480

RESUMO

BACKGROUND: Based on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice. METHODS: This retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected. RESULTS: Of the 133 patients, with a median age of 59.4 (16-83) years, 70 (52.6%) patients were male, 64 (48.1%) had pancreatic NET, 23 (17.3%) had ECOG PS ≥ 2, 41 (30.8%) had functioning tumours, 63 (47.7%) underwent surgery of the primary tumour, 45 (33.8%) had received prior chemotherapy, and 115 (86.5%) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5% (6 months), 68.6% (12 months) and 57.0% (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3% (6 months), 73.0% (12 months), and 67.4% (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95% CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone. CONCLUSIONS: The combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities and suggests efficacy that should be explored in randomized prospective clinical trials.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Peptídeos Cíclicos/efeitos adversos , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos Transversais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Peptídeos Cíclicos/administração & dosagem , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Adulto Jovem
8.
Mol Cancer ; 11: 25, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22537194

RESUMO

BACKGROUND: Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC), and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. RESULTS: In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and -independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS) and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC) to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. CONCLUSIONS: We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and -independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Inibidores Enzimáticos/farmacologia , Glutamatos/farmacologia , Guanina/análogos & derivados , Melanoma/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Guanina/farmacologia , Humanos , Melanoma/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pemetrexede , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
9.
Tumori ; 96(3): 405-10, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20845800

RESUMO

AIMS AND BACKGROUND: Gemcitabine is an effective agent in pancreatic adenocarcinoma. Fixed-dose-rate gemcitabine has an interesting biological and clinical rationale, with successful results in previous studies. We conducted a trial to confirm efficacy and toxicity of fixed-dose-rate gemcitabine in patients with pancreatic or biliary tree adenocarcinoma. METHODS: Eligible patients with locally advanced or metastatic pancreatic or biliary tree adenocarcinoma received fixed-dose-rate gemcitabine at a dose of 1500 mg/m(2) at a rate of 10 mg/m(2)/min weekly for 3 weeks every 28 days. Efficacy measures were overall survival, response rate and progression-free survival. RESULTS: Sixty-two patients were enrolled, and 59 were assessable for response. Seven patients (11.3%) had a partial response, 26 stable disease (41.9%) and 26 progressive disease (41.9%). Median time to progression was 21 weeks and median overall survival, 37.71 weeks. Main toxicities were grade 3-4 neutropenia (45.2%) and grade 2-3 asthenia (54.8%). No toxic deaths were documented. CONCLUSIONS: Fixed-dose-rate gemcitabine has a relevant antitumor activity but with significant toxicity. It represents an interesting schedule and could be combined with other biological or chemotherapeutic agents.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Análise de Variância , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias do Sistema Biliar/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Resultado do Tratamento , Gencitabina
10.
J Biomed Opt ; 14(2): 024006, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19405736

RESUMO

To study the radiation emitted by the human skin, the emissivity of its surface must be known. We present a new approach to measure the emissivity of the human skin in vivo. Our method is based on the calculation of the difference of two infrared images: one acquired before projecting a CO(2) laser beam on the surface of the skin and the other after such projection. The difference image contains the radiation reflected by the skin, which is used to calculate the emissivity, making use of Kirchhoff's law and the Helmholtz reciprocity relation. With our method, noncontact measurements are achieved, and the determination of the skin temperature is not needed, which has been an inconvenience for other methods. We show that it is possible to make determinations of the emissivity at specific wavelengths. Last, our results confirm that the human skin obeys Lambert's law of diffuse reflection and that it behaves almost like a blackbody at a wavelength of 10.6 microm.


Assuntos
Algoritmos , Temperatura Cutânea/fisiologia , Pele/efeitos da radiação , Espectrofotometria Infravermelho/métodos , Termografia/métodos , Relação Dose-Resposta à Radiação , Raios Infravermelhos , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
PLoS One ; 9(10): e109659, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25310221

RESUMO

The biological roles of estrogen receptor 1 (ERS1), estrogen receptor 2 (ERS2), and aromatase (CYP19A1) genes in the development of non-small cell lung cancer (NSCLC) is unclear, as is the use of their expression as a prognostic factor. The aim of this study was to investigate the prognostic value of estrogen receptors and aromatase mRNA expression, along with aromatase protein concentration, in resected NSCLC patients. Tumor and non-tumor lung tissue samples were analyzed for the mRNA expression of ERS1, ERS2 and CYP19A1 by RT-PCR. Aromatase concentration was measured with an ELISA. A total of 96 patients were included. ERS1 expression was significantly higher in non-tumor tissue than in tumor samples. Two gene expression categories were created for each gene (and protein): high and low. ERS1 high category showed increased overall survival (OS) when compared to the low expression category. Aromatase protein concentration was significantly higher in tumor samples. Higher ERS1 expression in tumor tissues was related to longer overall survival. The analysis of gene expression combinations provides evidence for longer OS when both ERS1 and ERS2 are highly expressed. ESR1, alone or in combination with ERS2 or CYP19A1, is the most determining prognostic factor within the analyzed 3 genes. It seems that ERS1 can play a role in NSCLC prognosis, alone or in combination with other genes such as ERS2 or Cyp19a1. ERS2 in combination with aromatase concentration could have a similar function.


Assuntos
Aromatase/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Taxa de Sobrevida
12.
PLoS One ; 8(5): e63338, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23675481

RESUMO

Although treatment options for cancer patients are increasing every year, the drug resistance problem remains very present. It is very difficult to find a drug that acts equally on tumours of the same histology as the individual's genetic characteristics often determine the response to treatment. Furthermore, tumours that initially respond to anti-tumour therapy are able to adapt and develop resistance to the drug, while others do not. In addition, this usually implies resistance development to agents to which the cells have not been exposed, a phenomenon called cross-resistance or multidrug resistance. Given this situation, it has been suggested that the most appropriate treatment would be able to act in parallel on multiple pathways constitutively altered in tumour cells. Pemetrexed is a multitargeted antifolate that exerts its activity against folate-dependent enzymes involved in de novo pyrimidine and purine synthesis. It is currently in use in combination with cisplatin against malignant pleural mesothelioma and non-squamous non-small cell lung cancer with favourable results. By real-time RT-PCR gene expression assays and restoration viability assays we demonstrated that Pemetrexed targets folate-dependent enzymes involved in de novo biosynthesis of purines differently depending on the intrinsic genetic characteristics of the tumour. These differences did not, however, interfere either with the initial response to the drug or with the activation of apoptotic pathways. In addition, these genetic fingerprints can differentiate two groups of tumours: those capable of developing resistance to antifolate, and not capable. These results may be useful to employ targets gene expression as resistance markers, a valuable tool for identifying patients likely to receive combination therapy to prevent the development of resistance.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Antagonistas do Ácido Fólico/farmacologia , Regulação Neoplásica da Expressão Gênica , Glutamatos/farmacologia , Guanina/análogos & derivados , Timidilato Sintase/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Guanina/farmacologia , Humanos , Especificidade de Órgãos , Pemetrexede , Purinas/antagonistas & inibidores , Purinas/biossíntese , Pirimidinas/antagonistas & inibidores , Pirimidinas/biossíntese , Timidilato Sintase/antagonistas & inibidores , Timidilato Sintase/metabolismo
13.
Rev. ADM ; 73(5): 255-262, sept.-oct. 2016. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-835303

RESUMO

Introducción: Los procedimientos de acabado y pulido de las restauraciones dentarias son fases determinantes en la práctica odontológica,ya que las superficies bien acabadas y pulidas aumentan la longevidadde la restauración, disminuyen la acumulación de placa y reducen las modificaciones del color marginal a la restauración y superficie. Objetivo: El propósito de este estudio fue evaluar tres diferentes sistemas de pulido: discos Sof-Lex, copas pulidoras Jiff y y sistema de un solopaso OptraPol, en función de la superficie obtenida en tres marcas deresinas estéticas nanohíbridas para zona anterior y posterior...


Introduction: The procedures for finishing and polishing dental restorations are crucial phases in dental practice, as well-fi nished andwell-polished surfaces increase the longevity of the restoration andreduce the buildup of plaque and marginal color changes in both therestoration and the surface. Objective: The purpose of this study wasto evaluate three diff erent polishing systems: Sof-Lex™, Jiff y® polishercups, and the OptraPol one-step system, based on the surface obtainedusing three brands of cosmetic nanohybrid resins in the anterior and posterior regions...


Assuntos
Estética Dentária , Nanoestruturas , Polimento Dentário/métodos , Resinas Compostas/química , Propriedades de Superfície , Análise de Variância , Teste de Materiais , Microscopia de Força Atômica/métodos , Interpretação Estatística de Dados
16.
Rev. chil. pediatr ; 70(5): 405-14, oct. 1999. tab, graf
Artigo em Espanhol | LILACS | ID: lil-263497

RESUMO

Un grupo oncológico pediátrico nacional, PINDA, reporta el primer protocolo prospectivo, no randomizado, para tratamiento de la leucemia linfoblástica (LLA), usando una versión modificada del protocolo de Berlín-Frankfurt-Munster (LLA BFM 86). Los objetivos de este estudio fueron clasificar inmunofenotipos, disminuir radioterapia de cráneo y comprobar si este protocolo podía mejorar la sobrevida de nuestros pacientes. Procedimiento: desde junio 1987 a junio 1992 se registraron 444 pacientes, no seleccionados; de ellos 425 fueron evaluables. La terapia fue estratificada según riesgo: riesgo bajo (RB), riesgo alto (RA) y riesgo muy alto (RMA). Los pacientes en RB y RA recibieron inducción con protocolo I, consolidación con protocolo M (RMA usó protocolo E), reinducción con protocolo II y mantención. Todos recibieron tratamiento de prefase con prednisona oral y metotrexato (MTX) intratecal. Radioterapia de cráneo solo en RA y RMA (12-18 Gy). Los siguientes cambios se introdujeron al protocolo LLA BFM 86: en protocolo M 1 g/m² en vez de 5 g/m²; en protocolo E, 1 g/m² de citarabina en vez de 2 g/m², la mitoxantrona e ifosfamida fueron sustituidas por teniposido y ciclofosfamida. Resultados: inmunofenotipo: LLA común 67,4 por ciento, LLA proB 14 por ciento, LLA T 10 por ciento, LLA preB 4,3 por ciento. La frecuencia de sobrevida libre de eventos (SLE) global a 5 años fue 60 por ciento ñ 2 por ciento error standard; según riesgo fue: RB 75 por ciento, RA 62 por ciento, RMA 28 por ciento con una mediana de seguimiento de 6,5 años (rango 4,5 - 9,5 años). La incidencia acumulada de recaída en sistema nervioso central SNC fue 5,4 por ciento. Conclusión: hemos tenido éxito en realizar un estudio a nivel nacional. Nuestra estrategia para adaptar el protocolo BFM fue efectiva para mejorar la SLE. La distribución por fenotipos es similar a otras series


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Protocolos de Quimioterapia Combinada Antineoplásica , Protocolos Clínicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Chile , Irradiação Craniana , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Países em Desenvolvimento , Intervalo Livre de Doença , Imunofenotipagem/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Metotrexato/farmacologia , Prednisona/farmacologia , Prognóstico , Teniposídeo/administração & dosagem
17.
Bol. Hosp. Viña del Mar ; 42(4): 237-44, 1986.
Artigo em Espanhol | LILACS | ID: lil-69764

RESUMO

Se analiza las posibilidades terapéuticas, actualmente aceptadas o en estudio, en los pacientes portadores de PTI refractario (definido como aquél que no ha respondido a esplenectomía y esteroides suprarrenales). Considerando que la trombocitopenia depende de la producción de anticuerpos antiplaquetarios, su unión a los trombocitos y la destrucción de éstos por los macrófagos del sistema retículoendotelial, se analiza el uso de fármacos que rompen esta cadena de eventos y pueden provocar mejoría del cuadro clínico. Entre éstos, se discute la utilidad de inmunosupresores (ciclofosfamida - azatioprina - vincristina - vinblastina y colchicina) administrados por distintas vías y con diversos fundamentos fisiopatológicos; se revisa experiencia en el uso de gamaglobulinas intravenosas; se menciona el uso del anabólico Danazol y sus posibilidades. Brevemente, se toca el uso de plasmaféresis y transfusión de plaquetas, como terapias de apoyo y se pretende dar una visión global que permite escoger un método de trabajo en el tratamiento de estos enfermos


Assuntos
Criança , Humanos , Púrpura Trombocitopênica/tratamento farmacológico , Imunização Passiva , Imunossupressores/uso terapêutico
18.
Bol. Hosp. Viña del Mar ; 42(4): 245-9, 1986. tab
Artigo em Espanhol | LILACS | ID: lil-69765

RESUMO

En una revisión de las fichas clínicas de 158 niños con Fiebre Tifoidea, acumulados en tres años, se analiza el hemograma en relación al tiempo de enfermedad y edad de los pacientes, incluyendo sólo aquellos confirmados bacteriológicamente: 87 casos. Se comprueba que en los lactantes el hemograma no es específico y que en el niño mayor de 2 años, la mayoría: 79% presentaba recuentos leucocitarios superiores a 5.000 por mm3; 92% presentaba aneosinofilia; el 55% un porcentaje de baciliformes sobre 10% y, cerca de un 37%, el porcentaje era mayor de 30% de baciliformes. La serie roja no se encontró alterada y la VHS está levemente elevada. No se encontró que hubiera correlación entre leucopenia y evolución menor de una semana


Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Humanos , Contagem de Leucócitos , Febre Tifoide/sangue , Contagem de Células Sanguíneas , Granulócitos
19.
Rev. chil. pediatr ; 65(1): 28-31, ene.-feb. 1994. ilus
Artigo em Espanhol | LILACS | ID: lil-140465

RESUMO

La anemia del recién nacido pretérmino que ingresa a las UCIS neonatales suele requerir de múltiples transfusiones de glóbulos rojos, con el consiguiente riesgo que esta práctica implica. Con el objeto de disminuir el número de transfusiones, se evaluó el efecto de eritropoyetina humana recombinante RH-EPO, 150 U/kg dos veces por semana, durante seis semanas, en ocho recién nacidos de bajo peso y siete controles de semejantes características clínicas que recibieron placebo, asignados al azar a cada grupo. El número de transfusiones realizadas 0,38 vs. 2,28; p<0,001 y el volumen de glóbulos rojos transfundidos 6,6 vs. 40,85 ml; p<0,001, en cada niño, a lo largo de las seis semanas de seguimiento, fueron significativamente menores en los niños tratados que en los controles, si bien la evolución del hematrocito y el recuento de retinoculocitos fue algo mayor, p: ns, en los niños que recibieron eritropoyetina


Assuntos
Recém-Nascido , Eritropoetina/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Anemia Neonatal/tratamento farmacológico , Eritropoetina/farmacologia , Placebos/administração & dosagem , Reticulócitos , Transfusão de Componentes Sanguíneos/métodos
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