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1.
Nat Med ; 26(3): 408-417, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32161403

RESUMO

The diagnosis of lymphomas and leukemias requires hematopathologists to integrate microscopically visible cellular morphology with antibody-identified cell surface molecule expression. To merge these into one high-throughput, highly multiplexed, single-cell assay, we quantify cell morphological features by their underlying, antibody-measurable molecular components, which empowers mass cytometers to 'see' like pathologists. When applied to 71 diverse clinical samples, single-cell morphometric profiling reveals robust and distinct patterns of 'morphometric' markers for each major cell type. Individually, lamin B1 highlights acute leukemias, lamin A/C helps distinguish normal from neoplastic mature T cells, and VAMP-7 recapitulates light-cytometric side scatter. Combined with machine learning, morphometric markers form intuitive visualizations of normal and neoplastic cellular distribution and differentiation. When recalibrated for myelomonocytic blast enumeration, this approach is superior to flow cytometry and comparable to expert microscopy, bypassing years of specialized training. The contextualization of traditional surface markers on independent morphometric frameworks permits more sensitive and automated diagnosis of complex hematopoietic diseases.


Assuntos
Leucemia/diagnóstico , Leucemia/patologia , Linfoma/diagnóstico , Linfoma/patologia , Análise de Célula Única/métodos , Células-Tronco Hematopoéticas/patologia , Humanos , Laminas/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Células Mieloides/patologia , Proteínas R-SNARE/metabolismo
2.
PLoS One ; 15(2): e0229352, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084225

RESUMO

INTRODUCTION: Heel pricks are performed on newborns for diagnostic screenings of various pre-symptomatic metabolic and genetic diseases. Excess blood is spotted on Guthrie cards and archived by many states in biobanks for follow-up diagnoses and public health research. However, storage environment may vary across biobanks and across time within biobanks. With increased applications of DNA extracted from spots for genetic studies, identifying factors associated with genotyping success is critical to maximize DNA quality for future studies. METHOD: We evaluated 399 blood spots, which were part of a genome-wide association study of childhood leukemia risk in children with Down syndrome, archived at the Michigan Neonatal Biobank between 1992 and 2008. High quality DNA was defined as having post-quality control call rate ≥ 99.0% based on the Illumina GenomeStudio 2.0 GenCall algorithm after processing the samples on the Illumina Infinium Global Screening Array. Bivariate analyses and multivariable logistic regression models were applied to evaluate effects of storage environment and storage duration on DNA genotyping quality. RESULTS: Both storage environment and duration were associated with sample genotyping call rates (p-values < 0.001). Sample call rates were associated with storage duration independent of storage environment (p-trend = 0.006 for DBS archived in an uncontrolled environment and p-trend = 0.002 in a controlled environment). However, 95% of the total sample had high genotyping quality with a call rate ≥ 95.0%, a standard threshold for acceptable sample quality in many genetic studies. CONCLUSION: Blood spot DNA quality was lower in samples archived in uncontrolled storage environments and for samples archived for longer durations. Still, regardless of storage environment or duration, neonatal biobanks including the Michigan Neonatal Biobanks can provide access to large collections of spots with DNA quality acceptable for most genotyping studies.


Assuntos
DNA/análise , Teste em Amostras de Sangue Seco/métodos , Genoma Humano , Estudo de Associação Genômica Ampla/métodos , Leucemia/diagnóstico , Triagem Neonatal/métodos , Feminino , Genótipo , Humanos , Recém-Nascido , Leucemia/genética , Masculino , Polimorfismo de Nucleotídeo Único , Manejo de Espécimes
3.
Acta Cytol ; 64(1-2): 71-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31063996

RESUMO

In the era of smaller and smaller biopsies submitted to pathology departments for diagnosis and the advent of personalized medicine, it has become imperative to efficiently and effectively use patient material to reach individualized, actionable diagnoses. The use of fine needle aspirates and core biopsies as acceptable methods for obtaining sufficient material for hematopoietic neoplasms under nonemergent conditions is debatable. There are, however, scenarios where only limited material is obtainable due to anatomic site, size of the lesion or condition of the patient. In these types of settings, thoughtful approaches and unconventional means are often necessary to reach a diagnosis. In this article, we describe three such scenarios and the unique tactics taken in each to obtain a personalized actionable diagnosis.


Assuntos
Biópsia por Agulha Fina/métodos , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias Hematológicas/patologia , Leucemia/patologia , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Idoso , Feminino , Neoplasias Hematológicas/diagnóstico , Humanos , Leucemia/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino
4.
Support Care Cancer ; 28(1): 35-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31444641

RESUMO

Impaired cardiovascular and autonomic function during treatment and during recovery from leukemia has been indicated. In this context, heart rate variability (HRV) is a non-invasive measure that describes the oscillations of the intervals between consecutive heart beats (RR intervals), influenced by the autonomic nervous system. We intend to review literature showing HRV changes in leukemia subjects. The articles selected in the current review were attained up to March 2018, and the search was limited to articles in English language, published in peer-reviewed journals, with both adult and child age samples. The articles were investigated in the five electronic databases: PubMed, Physiotherapy Evidence Database (PEDro), Cochrane Clinical Trials, Scientific Electronic Library Online (SciELO), and Excerpta Medica dataBASE (EMBASE). Towards the end of the research, 9 studies were included. Subjects undergoing treatment for leukemia have reduced HRV, signifying decreased vagal control of heart rate. The subjects that undertook leukemia treatment and their survivors experienced a reduction in HRV with subsequent recovery, but the recovery time is ill defined. HRV is reduced in leukemia subjects who progress to neuropathy secondary to chemotherapy, accompanied by cardiac dysfunction. We advocate the use of HRV to evaluate autonomic function and decide the treatment to prevent autonomic impairment in leukemia subjects.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Cardiopatias/diagnóstico , Frequência Cardíaca/fisiologia , Leucemia/tratamento farmacológico , Leucemia/fisiopatologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Criança , Eletrocardiografia , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Leucemia/diagnóstico , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos
5.
FP Essent ; 485: 17-23, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31613564

RESUMO

Leukocytosis is defined as a white blood cell count greater than 11,000/mcL in nonpregnant adults. It is a common finding, and the differential diagnosis can be broadly divided into primary malignant diseases and secondary causes that are expected physiologic responses of the bone marrow. Infections and chronic inflammatory conditions are common causes of secondary leukocytosis. A thorough history, physical examination, and peripheral blood smear are the basis of the initial evaluation. Constitutional symptoms along with an abnormal peripheral blood smear result indicate the need for evaluation for malignancy. Patients with chronic leukemias usually present with less severe symptoms than patients with acute leukemias. Symptoms generally are gradual in onset. Acute leukemias should be recognized quickly because they may be associated with life-threatening complications. Urgent referral to a hematology subspecialist is indicated in cases of suspected acute leukemia.


Assuntos
Leucemia , Leucocitose , Adulto , Humanos , Leucemia/diagnóstico , Leucemia/terapia , Contagem de Leucócitos , Leucocitose/diagnóstico , Leucocitose/terapia
6.
Exp Hematol ; 77: 1-5, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31472170

RESUMO

Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise healthy individuals, an observation that is strongly associated with age. These genetic mutations are often found at high frequency, suggesting dominance of a mutant HSC clone. Expansion of clones carrying other mutations not associated with leukemia or larger chromosomal deletions was also observed. This clinical observation has been termed clonal hematopoiesis, a condition associated with increased risk of both hematological malignancy and cardiovascular disease. Here, we discuss the identification of clonal hematopoiesis and its implications on human health, based on the May 2019 International Society for Experimental Hematology New Investigator Committee Webinar.


Assuntos
DNA Tumoral Circulante , Neoplasias Hematológicas , Hematopoese/genética , Leucemia , Mutação , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Humanos , Leucemia/sangue , Leucemia/diagnóstico , Leucemia/genética
7.
Biosens Bioelectron ; 143: 111593, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442750

RESUMO

Accurate and sensitive detection of the Pax-5a gene is of great importance in the early diagnosis and prognosis of acute leukaemia. Herein, a label-free electrochemical sensing system was proposed for the detection of the acute leukaemia Pax-5a gene based on enzyme-assisted signal amplification to generate abundant G-quadruplex/hemin DNAzyme. The presence of Pax-5a can open the hairpin probe (HP), which acts as a template. Under the action of the restriction enzymes Nt.BbvCI and Klenow fragment polymerase, the target gene Pax-5a is cycled to open the HP; On the other hand, a large number of G-quadruplex sequences are produced. The resulting G-quadruplex sequence is capable of forming the G-quadruplex/hemin complex on the surface of the electrode in the presence of hemin. The ultrasensitive label-free electrochemical detection of Pax-5a can be realized via the G-quadruplex/hemin complex-catalysed reduction of H2O2, and the detection limit was estimated to be as low as 4.6 fM. In addition, the biosensor has good specificity and stability, and also has excellent detection capabilities in a complex substrate environment. Therefore, the sensor shows great potential in bioanalysis and clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Leucemia/diagnóstico , Fator de Transcrição PAX5/isolamento & purificação , DNA Catalítico/química , Quadruplex G , Humanos , Peróxido de Hidrogênio/química , Leucemia/genética , Limite de Detecção , Nanofios/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Fator de Transcrição PAX5/genética
8.
BMC Cancer ; 19(1): 703, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315607

RESUMO

BACKGROUND: Leukemia is a malignant neoplasm that arises from hematopoietic cells. The number of leukemia cases has dramatically increased from 297,000 to 437, 033 cases worldwide. As result, the the Saudi Cancer Registry ramked leukemia as the 5th type of cancer cases among both genders in Saudi Arabia. Data on the trend and incidence of leukemnia in Saudi Arabia is lacking. This study aims to report the trend and incidence of leukemia in Saudi Arabia using available data from the Saudi Cancer Registry (SCR), as a population-based cancer registry in the country over a period of 15 years (1999-2013). METHODS: Data of registered leukemia cases between years 1999-2013 were retrieved from the Saudi Council of Health, Saudi Cancer Registry. Data were coded using the International Classification of Diseases for Oncology (ICD-O). Main and essential variables were retrieved such as age, sex, years of incidence, residency, and histopathological type of leukemia. RESULTS: A total of 8712 cases of leukemia were analyzed in this study, 57.2% were males and 42.8% were females. Around 33.6% of cases were from the central region of Saudi Arabia. The most diagnosed type of leukemia was the Precursor B-cell lymphoblastic leukemia (18.7%), followed by Precursor cell lymphoblastic leukemia, NOS (17.3%) with equal percentage of reported cases between males and females in these subsets. CONCLUSION: Ove a period of 15 years, the trend of leukemia showed the likelihood of increase in rate particularly in males with highest incidence reported from the central region of Saudi Arabia which needs more investigation. Resources for diagnosis and treatment should be planned with more orientation toward the accurate diagnosis of leukemia to minimize the number of "none specific diagnosis".


Assuntos
Leucemia/diagnóstico , Leucemia/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Substância Cinzenta , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Adulto Jovem
9.
Vet Clin North Am Small Anim Pract ; 49(5): 781-791, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280902

RESUMO

Molecular diagnostics have revolutionized human oncology to allow early detection, targeted therapy, monitoring throughout treatment, and evidence of recurrence. By identifying genetic signatures associated with cancers, liquid biopsy techniques have been developed to diagnose and monitor cancer in noninvasive or minimally invasive ways. These techniques offer new opportunities for improving cancer screening, diagnosis, and monitoring the impact of therapy on the patients over time. Liquid biopsy also drives drug development programs. Similar diagnostics hold promise for comparable results in the veterinary field. Several noninvasive/minimally invasive techniques have been described in veterinary medicine that could be referred to as liquid biopsy.


Assuntos
Doenças do Cão/diagnóstico , Biópsia Líquida/veterinária , Neoplasias/veterinária , Animais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/genética , Cães , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/veterinária , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/veterinária , Biópsia Líquida/métodos , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/veterinária , Masculino , Terapia de Alvo Molecular/veterinária , Mutação , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias Uretrais/diagnóstico , Neoplasias Uretrais/genética , Neoplasias Uretrais/veterinária , Neoplasias da Bexiga Urinária/veterinária
10.
Eur J Oncol Nurs ; 41: 49-55, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31358257

RESUMO

PURPOSE: This study explores how newly diagnosed patients with acute leukemia (AL) experience the diagnosis and the initial treatment, and their need and preferences for social support. METHODS: Explorative semi-structured individual interviews were carried out in patients with AL (n = 18) four to sixteen weeks post diagnosis. Thematic analysis was used to analyze the qualitative interview data. RESULTS: Identified themes were 1) Jolted by the diagnosis, and subtheme Loss of personal autonomy; 2) Restoring normality in everyday life, and subtheme Facing a new social identity; and 3) A lifeline of hope. Being newly diagnosed with AL was experienced as traumatic, which negatively affected personal autonomy and everyday life. There was a pressing need to restore a sense of normality in everyday life while managing a new social identity as a cancer patient. Social support from family, friends and other patients were invaluable and experienced as an important lifeline. CONCLUSION: Receiving a life threatening diagnose and undergoing chemotherapeutic treatment had a negative impact on everyday life which required re-establishing daily life activities. This increased the need for social support which had a distinct role in facilitating the patients' coping strategy. CLINICAL IMPLICATIONS: It is important to support and strengthen the patient's social network from the time of diagnosis. Future studies should examine the feasibility and benefit of experienced-based social support from peers (former patients) to patients with AL.


Assuntos
Doença Aguda/psicologia , Adaptação Psicológica , Leucemia/diagnóstico , Leucemia/psicologia , Leucemia/terapia , Determinação de Necessidades de Cuidados de Saúde , Pacientes/psicologia , Apoio Social , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Adulto Jovem
12.
Pediatr Blood Cancer ; 66(9): e27873, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207026

RESUMO

INTRODUCTION: In order to describe relapsed B-cell non-Hodgkin lymphoma and mature acute leukemia in children/adolescents treated with the Lymphomes Malins B (LMB) regimen and their outcome in the rituximab era, relapses in the French LMB2001 study were reviewed. METHODS: Between February 2001 and December 2011, 33 patients out of 773 (4.3%) relapsed; 27 had Burkitt lymphoma and six large B-cell histology. Median age at diagnosis was 10.1 years. One patient was initially treated in risk group A, 21 in group B, and 11 in group C. RESULTS: Median time to relapse after diagnosis was 4.5 months (range 2.4-13.6). Thirty-two patients received salvage therapy. Twenty-seven received rituximab mainly in addition to high-dose cytarabine and etoposide (n = 18) and/or ifosfamide, carboplatin, and etoposide (n = 7). First-line salvage chemotherapy response rate was 66% with 47% being complete remission (CR). Twenty-one patients received high-dose chemotherapy (HDC) followed by autologous (n = 13) or allogeneic (n = 8) transplant. With a median follow-up of 6.8 years, the 5-year survival rate after relapse was 36.4% (95% confidence interval [CI] 22-53%). Twelve patients were still alive; all but one (group A) received consolidation treatment. Achieving CR before consolidation was significantly associated with better survival, with a 5-year survival rate of 75% (95% CI 46.8-91.1%) for patients in CR before HDC, 33% (95% CI 9.7-70%) for patients in partial remission, and 0% for nonresponders (P = .033). CONCLUSION: Survival of children/adolescents with mature B-cell lymphoma/leukemia remains poor after relapse with no apparent improvement with rituximab. Response rates to salvage chemo-immunotherapies are insufficient and new drugs are urgently needed to improve disease control.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt , Leucemia , Linfoma Difuso de Grandes Células B , Doença Aguda , Adolescente , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/mortalidade , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , França , Humanos , Ifosfamida/administração & dosagem , Lactente , Leucemia/diagnóstico , Leucemia/tratamento farmacológico , Leucemia/mortalidade , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Estudos Prospectivos , Recidiva , Rituximab/administração & dosagem , Taxa de Sobrevida
13.
Sensors (Basel) ; 19(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058824

RESUMO

Label-free evaluation and monitoring of living cell conditions or functions by means of chemical and/or physical sensors in a real-time manner are increasingly desired in the field of basic research of cells and clinical diagnosis. In order to perform multi-parametric analysis of living cells on a chip, we here developed a surface plasmon resonance (SPR) imaging (SPRI)-impedance sensor that can detect both refractive index (RI) and impedance changes on a sensor chip with comb-shaped electrodes. We then investigated the potential of the sensor for label-free and real-time analysis of living cell reactions in response to stimuli. We cultured rat basophilic leukemia (RBL)-2H3 cells on the sensor chip, which was a glass slide coated with comb-shaped electrodes, and detected activation of RBL-2H3 cells, such as degranulation and morphological changes, in response to a dinitro-phenol-conjugated human serum albumin (DNP-HSA) antigen. Moreover, impedance analysis revealed that the changes of impedance derived from RBL-2H3 cell activation appeared in the range of 1 kHz-1 MHz. Furthermore, we monitored living cell-derived RI and impedance changes simultaneously on a sensor chip using the SPRI-impedance sensor. Thus, we developed a new technique to monitor both impedance and RI derived from living cells by using a comb-shaped electrode sensor chip. This technique may enable us to clarify complex living cell functions which affect the RI and impedance and apply this to medical applications, such as accurate clinical diagnosis of type I allergy.


Assuntos
Técnicas Biossensoriais , Fenômenos Fisiológicos Celulares , Rastreamento de Células/métodos , Diagnóstico por Imagem/métodos , Animais , Humanos , Leucemia/diagnóstico , Leucemia/patologia , Ratos , Ressonância de Plasmônio de Superfície
14.
BMJ Case Rep ; 12(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31129636

RESUMO

A female aged 84 years with a history of Clostridium difficile-associated diarrhoea presented from an extended care facility with altered mental status and respiratory distress. She was haemodynamically unstable and initial laboratory results revealed hyperleucocytosis (110.3×109/L). The presence of immature myeloid precursors, thrombocytopenia and respiratory distress, raised concern for an acute leukaemic process requiring emergent leucapheresis. However, on evaluation of the peripheral smear, prominent left shift and toxic granulation were noted, along with absence of blast cells. Considering her history of C. difficile infection, a CT scan of the abdomen and pelvis was obtained, which was suggestive of toxic megacolon. She was taken to the operating room for emergent colectomy. The pathology specimen showed pseudomembrane formation consistent with fulminant C. difficile infection. She was treated with oral vancomycin and intravenous metronidazole, followed by clinical improvement and resolution of leucocytosis and thrombocytopenia.


Assuntos
Leucocitose/sangue , Leucocitose/diagnóstico , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Infecções por Clostridium/complicações , Infecções por Clostridium/tratamento farmacológico , Colectomia , Diagnóstico Diferencial , Feminino , Humanos , Leucemia/diagnóstico , Leucocitose/tratamento farmacológico , Leucocitose/patologia , Megacolo Tóxico/diagnóstico por imagem , Megacolo Tóxico/etiologia , Megacolo Tóxico/cirurgia , Metronidazol/administração & dosagem , Tomografia Computadorizada por Raios X , Vancomicina/administração & dosagem
16.
J Coll Physicians Surg Pak ; 29(6): S59-S61, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142425

RESUMO

Hyper eosinophilic syndrome (HES) is a rare condition with a potential for morbidity and mortality, if left untreated. Therefore, it is important to highlight it, as often these cases are misdiagnosed and mismanaged, specially when presenting with an atypical initial presentation. This case report describes an unusual initial clinical presentation of HES. Patient was a 75-year lady presenting to Rheumatology Clinic with short duration of fever and polyarthritis. Joint aspiration showed purulent fluid with a cell count of 61,000/mm3 with predominant neutrophils and eosinophils. Her peripheral blood also showed a high white blood cell (WBC) count (80,700/mm3 with 73% eosinophils). Her workup for eosinophilic leukemia was negative, so a diagnosis of HES was made. She was initiated on corticosteroids and hydroxycarbamide as first-line therapy. Unfortunately, the patient was unresponsive to steroids with her WBC count rising to 130,000/mm3 and her clinical course was complicated by cardiac failure and peripheral neuropathy. Improvement in arthritis and peripheral eosinophilia was noted after she was given imatinib and stabilised clinically.


Assuntos
Artrite/diagnóstico , Síndrome Hipereosinofílica/diagnóstico , Leucemia/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Artrite/tratamento farmacológico , Artrite Infecciosa , Feminino , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/uso terapêutico , Leucemia/tratamento farmacológico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Resultado do Tratamento
17.
Mikrochim Acta ; 186(4): 241, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30868262

RESUMO

The activity of terminal deoxynucleotidyl transferase (TdTase) is a biomarker for routine diagnosis of acute leukemia. A method has been developed for the determination of TdTase activity. It is based on the use of silver nanoclusters (AgNCs) whose yellow fluorescence is enhanced by an in-situ grown DNA tail of TdTase-polymerized and guanine-rich DNA at the 3' end of a hairpin DNA. The fluorescence, best measured at excitation/emission peaks of 530/585 nm, increases linearly in the 1 to 35 mU mL-1 TdTase activity range. The detection limit is 0.8 mU mL-1. The method is cost-efficient, selective and convenient. It integrates enhancement of the fluorescence of AgNCs and target recognition into a single process. Graphical abstract Schematic presentation of a method for determination of TdTase activity. It is based on AgNCs fluorescence enhanced by in-situ grown TdTase-polymerized G-rich DNA tail. The method integrates AgNCs fluorescence enhancement and the target recognition into a single process.


Assuntos
DNA Nucleotidilexotransferase/sangue , DNA/química , Ensaios Enzimáticos/métodos , Nanopartículas Metálicas/química , Sequência de Bases , Biomarcadores/sangue , Técnicas Biossensoriais/métodos , DNA/genética , Fluorescência , Humanos , Sequências Repetidas Invertidas , Leucemia/diagnóstico , Limite de Detecção , Prata/química , Espectrometria de Fluorescência/métodos
18.
PLoS One ; 14(3): e0213621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30861043

RESUMO

Based in high sensitivity and specificity reported recently in detection of the cancer, the technique of Raman spectroscopy is proposed to discriminate between breast cancer, leukemia and cervical cancer using blood serum samples from patients officially diagnosed. In order to classify Raman spectra, clustering method known as Super Paramagnetic Clustering based on statistical physics concepts with a stochastic approach was implemented. Comparing firstly average Raman spectra of the three cancers, some peaks that allowed differentiating one cancer from other were identified, however, other peaks allowed concluding that there are biochemical similarities among them. According to these spectra, the band associated with amide I (1654 cm-1) and one of two shoulders assigned to amide III (1230-1282 cm-1) allowed discriminating leukemia from breast and cervical cancer, whereas band 714 cm-1 (polysaccharides) achieves to differentiate cervical cancer from leukemia and breast cancer, and bulged region, 1040 - 1100 cm-1 (phenylalanine, phospholipid) discriminated breast cancer from leukemia and cervical cancer. Subsequently, Super Paramagnetic Clustering method was applied to Raman spectra to study similarity relationships between cancers based on the biochemical composition of serum samples. Finally, as a cross check method, the standard method to classify Raman spectra of breast cancer, leukemia and cervical cancer, known as principal components analysis, was used showing excellent agreement with results of Super Paramagnetic Clustering method. Preliminary results demonstrated that Raman spectroscopy and Super Paramagnetic Clustering method can be used to discriminate between breast cancer, leukemia and cervical cancer samples using blood serum samples.


Assuntos
Neoplasias da Mama/diagnóstico , Leucemia/diagnóstico , Neoplasias/diagnóstico , Análise Espectral Raman , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Algoritmos , Amidas , Criança , Análise por Conglomerados , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Componente Principal , Software , Processos Estocásticos , Adulto Jovem
19.
Med Confl Surviv ; 35(2): 144-170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30821174

RESUMO

Increased incidences of childhood acute leukaemia were noted among survivors of the atomic bombings of Hiroshima and Nagasaki. In Western societies, Childhood Acute Lymphoblastic Leukaemia has a distinct epidemiology peaking at 3 years old. Exposure to ionising radiation is an established hazard but it is difficult to gauge the precise risk of less than 100 mSv. Since 1983 significant leukaemia incidences have been reported among families residing near nuclear installations. The target cells (naïve neonatal lymphocytes) get exposed to multiple xenobiotic challenges and undergo extraordinary proliferation and physiological somatic genetic change. Population movements and ionising radiation are considered taking account of updated understanding of radiation biology, cancer cytogenetics and immunological diversity. Double Strand Breaks in DNA arise through metabolic generation of Reactive Oxygen Species, and nearly always are repaired; but mis-repairs can be oncogenic. Recombinant Activating Gene enzymes in rapidly dividing perinatal pre-B lymphocytes being primed for antibody diversity are targeted to Signal Sequences in the Immunoglobulin genes. off target pseudo-sequences may allow RAG enzymes to create autosomal DSBs which, when mis-repaired, become translocated oncogenes. Immunogens acting by chance at crucial stages may facilitate this. In such circumstances, oncogenic DSBs from ionising radiation are less likely to be significant.


Assuntos
Dano ao DNA , Sistema Imunitário , Leucemia/genética , Leucemia/imunologia , Radiação Ionizante , Translocação Genética , Criança , Pré-Escolar , Quebras de DNA de Cadeia Dupla , Dano ao DNA/efeitos da radiação , Diploide , Exposição Ambiental , Humanos , Lactente , Recém-Nascido , Leucemia/diagnóstico , Leucemia/epidemiologia , Centrais Nucleares , Doses de Radiação , Radiografia
20.
Mol Omics ; 15(2): 117-129, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30720033

RESUMO

Protein isoforms are structurally similar proteins produced by alternative splicing of a single gene or genes from the same family. Isoforms of a protein can perform the same, similar, or even opposite biological functions. A previous study identified principal isoforms of proteins based on the extent of interactions per isoform in a functional relationship network, focusing on data from normal tissues. Additionally, the expression levels of specific isoforms of various genes associated with tumorigenesis and prognosis are frequently altered in tumors compared with those in normal tissues. In this study, we aimed to identify higher degree isoforms (HDIs) of multi-isoform genes (MIGs) in cancer by applying a meta-analytical framework to calculate co-expression between each pair of isoforms in two large datasets of RNA-seq profiles from breast cancer, lung cancer, leukemia, and colon cancer cell lines. Then, we compared HDIs with isoforms identified by proteomic data and prognostic and predictive evidence in various cancers. In addition, we separately analyzed the associations between HDIs and non-HDIs (nHDIs) of the same genes according to transcript expression and drug responses in various cancer type cell lines. Collectively, these results indicated the complex properties of HDIs per gene identified by cancer type-based isoform-isoform co-expression networks and showed the potential of HDIs as novel therapeutic targets for cancer treatment.


Assuntos
Processamento Alternativo/genética , Neoplasias da Mama/genética , Neoplasias do Colo/genética , Leucemia/genética , Neoplasias Pulmonares/genética , Isoformas de Proteínas/genética , Biomarcadores Farmacológicos/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Neoplasias/genética , Prognóstico , Proteômica , RNA Neoplásico/genética
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