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1.
Biochem Pharmacol ; 171: 113713, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31733192

RESUMO

Oral cancer is a prevalent cancer in male worldwide. Oral potentially malignant disorders (OMPDs) are the oral mucosa lesions that have high malignant transformation rate to oral cancer. The mainstay for OMPDs treatment includes carbon dioxide (CO2) laser and surgery, which may lead to the side effects of scarring and impaired function of oral cavity in the patients and reduced their willingness to receive curative therapy. Therefore, developing a non-invasive and function-preserving therapy is clinically important. Since development of a novel chemotherapeutic drug requires a lot of time and cost, we applied the high-throughput screening (HTS) approach to identify new bioactivities for FDA-approved drugs, known as drug repurposing. Through this drug repurposing approach, we discovered that gentian violet (GV), which is well known for its antibacterial, antifungal, antihelminthic, antitrypanosomal and antiviral activities, was able to induce significant cell death in DOK oral precancerous cells through ROS production. Moreover, decreased phosphorylation of p53(Ser15) and NFκB(Ser536) was required for GV-induced cell death. In vivo, 3% GV orabase effectively suppressed the progression of DMBA-induced oral precancerous lesions. In conclusion, this new formulation of GV through drug repurposing has the potential to be further developed as a therapeutic drug for OPMD clinically.

2.
Prev Med ; 127: 105790, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398410

RESUMO

Malaria continues to be among the top causes of death in children and insecticide-treated nets (ITNs) are considered among the most effective malaria control methods. However, information on the association between universal ITN coverage and infant mortality is limited. A Cox proportional hazard model was applied to Malawi Demographic and Health Surveys to determine the association between ITN access and use and infant mortality between 2004 and 2015-2016. The overall infant mortality rate for the entire period was 47.9/1000 live births. Infants from the ITN-user households exhibited a lower risk of mortality [adjusted Hazard Ratio (aHR) = 0.61, 95% Confidence Interval (CI) = 0.44-0.85] than those from the ITN-nonuser households. Similarly, the infants from the high-access households exhibited a lower risk of death (aHR = 0.63, 95% CI = 0.46-0.86) than those from the no-access households. Infants from the ITN-user and high-access households exhibited a significantly lower risk of death (aHR = 0.57, 95% CI = 0.40-0.82) than those from the ITN-nonuser and no-access households. The relationship between ITN access and use and infant mortality was significant among female infants with a second or higher birth order and interval of ≥2 years. The findings of the present population-based study emphasized the importance of ITN access and use in providing optimal protection against malaria to infants in Malawi. Malaria control programs should ensure high ITN access and use in Malawi to reduce infant mortality.

3.
Tob Control ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164488

RESUMO

INTRODUCTION: This study aims to analyse the non-tax-induced price increasing strategies adopted by tobacco industry in Taiwan, a high-income country with comprehensive tobacco control policies but low tobacco taxes and a declining cigarette market. METHODS: Using governmental tax, price and inflation data, we analysed cigarette sales volume, affordability, affordability elasticity of demand, market share, pricing and net revenue of the top five tobacco companies in Taiwan from 2011 to 2016 when no tax increases occurred. RESULTS: Total revenue after tax grew significantly for all the major transnational tobacco companies between 2011 and 2016 at the expense of the state-owned Taiwan Tobacco and Liquor Corporation. In terms of market share, Japan Tobacco (JT) was the leading company, despite experiencing a small decline, while British American Tobacco and Imperial Brands remained stable, and Philip Morris International increased from 4.7% to 7.0%. JT adopted the most effective pricing strategy by increasing the real price of its two most popular brands (Mevius and Mi-Ne) and, at the same time, doubling the sales of its cheaper and less popular brand Winston by leaving its nominal retail price unaltered. CONCLUSIONS: Low and unchanged tobacco taxes enable tobacco companies to use aggressive pricing and segmentation strategies to increase the real price of cigarettes without making them less affordable while simultaneously maintaining customers' loyalty. It is crucial to continue monitoring the industry's pricing strategies and to regularly increase taxes to promote public health and to prevent tobacco industry from profiting at the expense of government revenues.

4.
Leuk Lymphoma ; : 1-6, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31225766

RESUMO

Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) (tDLBCL) has been traditionally associated with an aggressive course, but more recent studies have shown longer survivals. The clinical significance of concurrent FL at the time of diagnosis of DLBCL (cDLBCL/FL) is less clear. We compared outcomes of tDLBCL, cDLBCL/FL, and de novo DLBCL (dDLBCL) and then evaluated the impact of double hit (DH) rearrangements (MYC with BCL2 and/or BCL6) in these subgroups' outcomes. The progression free survival (PFS) and overall survival (OS) were not significantly different among the three groups (dDLBCL, tDLBCL, and cDLBCL/FL). The effect of DH on survival was then analyzed in two subgroups: (1) dDLBCL and (2) tDLBCL + cDLBCL/FL. PFS and OS were significantly shorter in lymphomas with DH in each of these two subgroups. We conclude that DH status drives outcomes in all DLBCLs, regardless of their transformation status.

5.
Hum Pathol ; 91: 1-10, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31125631

RESUMO

Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia that is defined by the presence of the translocations that mostly involve the RARA gene. The most frequent translocation is the t(15;17), which fuses the RARA gene with the PML gene. Previous studies have shown that other cooperative mutations are required for the development of APL after the initiating event of the t(15;17). In this study, we combined cytogenetics with next-generation sequencing and single-nucleotide polymorphism array to study the genetic complexity in 20 APL cases diagnosed in our institution. All but 3 cases had additional genetic aberrations. Our study demonstrated that somatic mutations are frequent events in APL. In addition to the previously reported recurrent cooperative mutations in the FLT3, WT1, and RAS genes, we identified mutations in several epigenetic modifiers, including TET2, EZH2, and DNMT3A, co-occurring with either FLT3 or WT1 mutations. Mutations of the WT1 gene and chromosome 11p copy neutral loss of heterozygosity affecting WT1 are present in a third of the cases in our series. Two-thirds of APL cases in our study demonstrated a global reduction but focal accumulation of H3K27 methylase (H3K27me) expression, indicating a disorganized chromatin methylation pattern with generally more accessible chromatin status. Our study confirmed genetic complexity of APL and revealed that epigenetic aberrations are more common than previously expected. Although epigenetic modulation is not a common treatment strategy in APL, targeting this pathway may have some clinical utility in refractory or relapsed APL cases.

6.
Acta Cytol ; : 1-10, 2019 May 07.
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.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30935027

RESUMO

A growing literature indicates that electronic cigarette use increases the risk of subsequent initiation of conventional smoking among cigarette-naïve adolescents in several Western countries. This research assesses the same relationship in an Asian country, Taiwan. The Taiwan Adolescent to Adult Longitudinal Study is a school-based survey that was carried out in two waves in 2014 (baseline) and in 2016 (follow-up). It employs probability sampling to create nationally representative samples of students in junior high school (mean age 13, 7th grade at baseline) and in senior high school (mean age 16, 10th grade at baseline). Data from this survey were analyzed via logistic regression to estimate the association between ever use of e-cigarettes at baseline and smoking initiation at follow-up, accounting for susceptibility to smoking, socio-demographic profile, depression status, and peer support. Among the 12,954 cigarette-naïve students surveyed, those with e-cigarette experience at baseline exhibited higher odds of smoking initiation at follow-up (Odds Ratio = 2.14, 95% CI (1.66, 2.75), p < 0.001). For the first time, we confirmed, through a longitudinal survey, a prospective association between ever use of e-cigarettes and smoking initiation in an Asian adolescent population. The restrictive policy on e-cigarettes currently in force in Taiwan is justified to prevent both e-cigarette and cigarette use among adolescents.


Assuntos
Comportamento do Adolescente , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Fumar/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Instituições Acadêmicas , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Taiwan/epidemiologia , Produtos do Tabaco/estatística & dados numéricos
8.
Am J Trop Med Hyg ; 100(6): 1454-1465, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30994089

RESUMO

Early diagnosis and treatment of childhood fever, an important sign of potentially serious infections such as malaria, is essential for controlling disease progression, and ultimately, preventing deaths. This study examined individual- and community-level factors associated with treatment-seeking behaviors and promptness in these behaviors among caregivers of febrile under-five children in Malawi. The 2015-2016 Malawi Demographic Health Survey was used to analyze a nationally representative sample of 4,133 under-five children who had fever within 2 weeks before the survey. A multilevel logistic regression model was used to examine the association between individual- and community-level factors and treatment-seeking behaviors. Approximately 67.3% of the caregivers reported seeking treatment for their febrile child, whereas only 46.3% reported promptly seeking treatment. Children from communities with moderate and high percentages of educated caregivers were more likely to be taken for treatment (adjusted odds ratio [aOR] = 1.26, 95% CI = 1.01-1.58 and aOR = 1.31, 95% CI = 1.02-1.70, respectively) than those from communities with a low percentage of educated caregivers. Children from communities with moderate and high percentages of caregivers complaining about the distance to a health facility were less likely to be taken for treatment (aOR = 0.74, 95% CI = 0.58-0.96 and aOR = 0.67, 95% CI = 0.51-0.88, respectively). At the individual level, having a cough in the last 2 weeks, region, religion, and having better health behaviors in other health dimensions were associated with fever treatment-seeking behaviors among Malawian caregivers. Programs aimed at improving treatment-seeking behaviors should consider these factors and the regional variations observed in this study.

9.
Mol Biol Evol ; 36(6): 1148-1161, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30835262

RESUMO

Pyricularia is a fungal genus comprising several pathogenic species causing the blast disease in monocots. Pyricularia oryzae, the best-known species, infects rice, wheat, finger millet, and other crops. As past comparative and population genomics studies mainly focused on isolates of P. oryzae, the genomes of the other Pyricularia species have not been well explored. In this study, we obtained a chromosomal-level genome assembly of the finger millet isolate P. oryzae MZ5-1-6 and also highly contiguous assemblies of Pyricularia sp. LS, P. grisea, and P. pennisetigena. The differences in the genomic content of repetitive DNA sequences could largely explain the variation in genome size among these new genomes. Moreover, we found extensive gene gains and losses and structural changes among Pyricularia genomes, including a large interchromosomal translocation. We searched for homologs of known blast effectors across fungal taxa and found that most avirulence effectors are specific to Pyricularia, whereas many other effectors share homologs with distant fungal taxa. In particular, we discovered a novel effector family with metalloprotease activity, distinct from the well-known AVR-Pita family. We predicted 751 gene families containing putative effectors in 7 Pyricularia genomes and found that 60 of them showed differential expression in the P. oryzae MZ5-1-6 transcriptomes obtained under experimental conditions mimicking the pathogen infection process. In summary, this study increased our understanding of the structural, functional, and evolutionary genomics of the blast pathogen and identified new potential effector genes, providing useful data for developing crops with durable resistance.


Assuntos
Evolução Biológica , Genoma Fúngico , Família Multigênica , Pyricularia grisea/genética , Cromossomos Fúngicos , Metaloproteases/genética , Milhetes/microbiologia , Doenças das Plantas , Homologia de Sequência do Ácido Nucleico , Transcriptoma
10.
Diagn Pathol ; 14(1): 26, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922345

RESUMO

BACKGROUD: Myeloid sarcoma (MS) is a rare neoplasm of immature myeloid precursors that form tumor mass outside the bone marrow. The diagnosis of de novo MS can be challenging, particularly in patients with no prior history of hematologic malignancies or when MS involves unusual anatomic sites. CASE PRESENTATION: The patient was a 53-year-old woman with a history of uterine fibroids and vaginal bleeding for many years who presented with a vaginal wall mass. The tumor had histologic and phenotypic features of histiocytic sarcoma, however, overlapping with a possible extramedullary MS. Using a comprehensive genomic profiling, we were able to identify recurrent chromosomal aberrations associated with MS including a rare KMT2A-ELL fusion, losses of chromosomes 1p, 9, 10, 15, 18, and gain of chromosome 1q and mutations in FLT3 and PTPN11, and achived the final diagnosis of a de novo MS. The patient received standard treatment for acute myeloid leukemia regimen with stem cell transplantation and achieved complete remission. CONCLUSION: Our case illustrates the clinical utility of comprehensive genomic profiling in assisting the diagnosis or differential diagnosis of challenging MS or histiocytic sarcoma cases, and in providing important information in tumor biology for appropriate clinical management.


Assuntos
Aberrações Cromossômicas , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/diagnóstico , Proteína de Leucina Linfoide-Mieloide/genética , Sarcoma Mieloide/diagnóstico , Fatores de Elongação da Transcrição/genética , Feminino , Fusão Gênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/cirurgia , Pessoa de Meia-Idade , Sarcoma Mieloide/genética , Sarcoma Mieloide/patologia , Sarcoma Mieloide/cirurgia , Transplante de Células-Tronco , Resultado do Tratamento , Vagina/patologia , Vagina/cirurgia
11.
Sci Rep ; 9(1): 1071, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705320

RESUMO

Endogenous K. pneumoniae endophthalmitis (EKE) has a higher incidence among East Asians, and the most common infectious source of EKE is pyogenic liver abscess (PLA). We investigate the risk factors for poor visual outcomes in patients with PLA-related EKE. The retrospective medical records of 104 patients (120 eyes) diagnosed with PLA-related EKE between 1996 and 2015. In univariate logistic regression analysis, the risk factors for poor visual outcomes were initial visual acuity (VA) worse than counting fingers (CF) (p < 0.001), eye pain (p = 0.013), hypopyon (p = 0.003), ocular hypertension (p = 0.003), positive intraocular fluids cultures (p < 0.001), subretinal abscess (p = 0.025), unilateral involvement (p = 0.017), delayed ophthalmologic visit (p = 0.022), initially presented with ocular symptoms ahead of systemic symptoms (p < 0.001), and corneal edema (p < 0.001). Intravitreal dexamethasone reduced the requirement of enucleation or evisceration (p = 0.01). The multivariate logistic regression revealed that poor initial VA worse than CF (p = 0.004) and initially presented with ocular symptoms ahead of systemic symptoms (p = 0.007) were the significant independent factors for poor visual outcomes. Early diagnosis and prompt treatment may salvage useful vision in some eyes.

12.
Sci Total Environ ; 655: 958-967, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30609636

RESUMO

Hydrogel as commercial soil conditioner has the potential to improve soil properties and reduce water scarcity in growing plants. However, use of polyacrylamide-based hydrogel in agriculture pose potential human health hazards. Hydrogel systems were prepared from temperature-responsive methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) blended with potassium sulfate (K2SO4, K-containing fertilizer). Blended K2SO4 in hydrogels affects the hydrophobic interaction of MC and HPMC, and hydrogels prepared in 0.25 M K2SO4 decrease the gelation temperatures of MC and HPMC from 55.6 and 67.4 °C to 27.8 and 35.1 °C, respectively. The equilibrium swelling ratio (St) of MC and HPMC hydrogels was increased 15 times and hydrogels maintained a steady appearance. The swelling kinetics of the MC and HPMC hydrogels followed Schott's second-order model and kinetic parameters indicated that adding K2SO4 can improve the initial swelling rate. K2SO4 decreases the pore size of the MC and HPMC hydrogel from 26.8 and 21.5 µm to 14.7 and 14.2 µm. A plant growth assessment indicated inhibition in plant growth occurred without the application of the hydrogels. Adding K2SO4 increases mechanical properties of the hydrogels. Treatment with 0.5% hydrogel considerably improves the water-holding and water-retention capacities of sandy soil. The 20-20-20 fertilizer release results revealed at that at 35 °C and a pH below 7, the hydrogel systems reduce the release rate of the fertilizer. The best result was observed with the Korsmeyer-Peppas model, indicating that the fertilizer transport mechanism involves Fickian diffusion and swelling-controlled release. This study discovered that environmentally responsive cellulose-based hydrogels have potential for use as soil conditioners and as controlled release devices in horticulture and agriculture.

13.
J Affect Disord ; 242: 39-47, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30170237

RESUMO

BACKGROUND: Mental distress patterns in first-time or experienced mothers and fathers during the transition to parenthood have been inadequately studied. This longitudinal study thus investigated changes in depression, anxiety, and health-related quality of life in both parents from early pregnancy until 1 year postpartum. Parity effects were specifically examined. METHODS: In total, 531 pregnant women and their partners were recruited in Taiwan during early prenatal visits from 2011 to 2015, with five follow-ups from midpregnancy to 1 year postpartum. The participants' self-reported data were collected and analyzed using generalized estimating equation models. RESULTS: Maternal mental distress levels were highest at 1 month postpartum. During postpartum periods, depression scores increased and social relations domain scores decreased in men. Although mental distress levels were higher in mothers than in fathers, parity evidently affected men. Experienced fathers were independently associated with a 70% higher risk of perinatal depression (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.2-2.3) and anxiety (OR = 1.7, 95% CI = 1.2-2.6). Experienced fathers also exhibited significantly lower perinatal scores than first-time fathers in the physical health and social relations domains. LIMITATIONS: Selection of both parents in metropolitan areas with higher socioeconomic status may restrict the generalizability of our findings. CONCLUSIONS: In addition to maternal mental distress during the transition to parenthood, we highlighted experienced fathers' psychological difficulties throughout perinatal periods. Such trends may indicate unsatisfied needs and could guide timely intervention to prevent adverse consequences.


Assuntos
Transtornos de Ansiedade/psicologia , Transtorno Depressivo/psicologia , Pai/psicologia , Mães/psicologia , Qualidade de Vida/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Razão de Chances , Paridade , Período Pós-Parto , Gravidez , Estudos Prospectivos , Taiwan , Adulto Jovem
14.
Tob Control ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397030

RESUMO

INTRODUCTION: Adult smoking prevalence in Taiwan rapidly declined from 26.5% in 2005 to 20.0% in 2015. Nevertheless, future projections on smoking-attributable deaths and current per capita consumption do not paint an equally bright picture. METHODS: We used SimSmoke, a tobacco control simulation model to assess the impact of tax increases and other policies by predicting past and projecting over future decades smoking rates and smoking-attributable mortality. RESULTS: The model accurately depicts the decline in smoking prevalence observed in Taiwan from 2000 to 2015. Nonetheless, under the 'status quo' scenario, smoking-attributable mortality is projected to continue growing, peaking at 26 602 annual deaths in 2039 and cumulative deaths >1 million by 2044. By comparing projections with current policies with a counterfactual scenario based on the 2000 policy levels, SimSmoke estimates that tobacco control in Taiwan has been able to reduce smoking prevalence by 30% in 2015 with 450 000 fewer smoking-attributable deaths by 2060. Modified scenarios show that doubling the retail price of cigarettes and fully implementing the remaining MPOWER measures would avert approximately 45 000 lives by 2040 and 130 000 by 2060. CONCLUSIONS: Tobacco will be a leading cause of death in Taiwan for the coming decades, showing yet again the long-term consequences of smoking on public health. The MPOWER package, even if adopted at the highest level with a large tax increase, is unlikely to reduce smoking prevalence to the endgame goal of 5% in the next five decades.

15.
Arch Pathol Lab Med ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30444439

RESUMO

CONTEXT.­: The pathogenesis of primary ocular adnexal marginal zone lymphoma (POAMZL) remains unclear. The reported associations with Chlamydia psittaci infection and MYD88 mutations are highly variable. OBJECTIVE.­: To examine MYD88 L265P mutation in ocular marginal zone lymphomas and correlate with clinicopathologic features and Chlamydia infection. DESIGN.­: Presence of MYD88 L265P mutation and Chlamydia infection in lymphoma was analyzed by using sensitive polymerase chain reaction (PCR) methods. RESULTS.­: The MYD88 L265P mutation was identified in 8 of 22 POAMZLs (36%), including 2 of 3 cases in which PCR failed to detect clonal IGH gene rearrangement; none of the 4 secondary marginal zone lymphomas were positive. Test results for Chlamydia were negative in all cases. Patients with and without the MYD88 mutation had similar clinicopathologic features. CONCLUSIONS.­: The MYD88 mutational analysis provides important information in diagnostic workup of POAMZL. The frequent MYD88 mutation suggests a critical role of this aberration in the pathogenesis of POAMZL and may serve as a therapeutic target for patients with progressive disease.

16.
Malar J ; 17(1): 372, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340640

RESUMO

BACKGROUND: This study aimed to identify factors at individual and community level influencing insecticide-treated net (ITN) usage among groups of women of childbearing age (WOCBA) in Malawi. METHODS: Factors influencing ITN usage in Malawi were assessed through interviews with 16,130 WOCBA (15-49 years) across 850 communities who participated in the 2015-2016 Malawi Demographic Health Survey. Multilevel logistic regression analysis was used. RESULTS: ITN use was similar between pregnant women and non-pregnant women with children under 5 years (45.9% and 46.9%, respectively), but slightly lower among non-pregnant women without children under 5 years (39.1%). Both individual and community characteristics were associated with ITN use among WOCBA and varied significantly across subgroups. Specifically, non-pregnant women with children under 5 years living in communities where women had high autonomy in health care decisions had an 18% greater odds of using an ITN compared with those from communities where women had low health care autonomy (adjusted odds ratio [aOR] = 1.18; 95% confidence interval [CI] 1.00-1.38). Distance to health care facility influenced ITN usage among pregnant women; those who did not regard distance as a problem had a 44% greater odds of using an ITN than those for whom distance was seen as a problem (aOR = 1.44; 95% CI 1.09-1.89). Number of household members, region, urbanization, and community ITN coverage influenced ITN usage across all WOCBA groups. CONCLUSION: The findings confirmed the importance of assessing various factors affecting ITN usage among groups of WOCBA. Both individual- and community-level factors should be considered when designing and implementing ITN programmes in Malawi.

17.
Diagn Pathol ; 13(1): 78, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30322385

RESUMO

BACKGROUND: Transformation of follicular lymphoma most typically occurs as diffuse large B-cell lymphoma, however other forms of transformation such as classic Hodgkin lymphoma and lymphoblastic transformation can occur. Secondary malignant histiocytosis also represents a rare form of transformation, which is thought to occur due to a process of transdifferentiation whereby the lymphoma cells exhibit lineage plasticity and lose all evidence of B-cell phenotype and instead acquire the phenotype of a histiocytic neoplasm. Little is known about the underlying genetic alterations that occur during this unusual process. Comparative genetic analysis of pre- and post-transformation/transdifferentiation would be one tool by which we could better understand how this phenomenon occurs. CASE PRESENTATION: Here we report the clinical, immunophenotypic and genetic features of a rare case of secondary malignant histiocytosis, Langerhans cell-type (Langerhans cell sarcoma) arising from a previous low grade follicular lymphoma. FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. Comparative whole exome sequencing was then performed, which identified a KRAS p.G13D mutation in the LCS that was not present in the FL. CONCLUSIONS: This report highlights genetic alterations, in particular an acquired somatic KRAS mutation, that may occur during transdifferentiation, with additional significance of KRAS mutation as a possible therapeutic target in cases which otherwise would have limited treatment options.

18.
BMC Ecol ; 18(1): 31, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30189862

RESUMO

BACKGROUND: During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction. RESULTS: The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area. CONCLUSIONS: The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.

19.
JCI Insight ; 3(15)2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30089730

RESUMO

Acute myeloid leukemia (AML) patients with NPM1 mutations demonstrate a superior response to standard chemotherapy treatment. Our previous work has shown that these favorable outcomes are linked to the cytoplasmic relocalization and inactivation of FOXM1 driven by mutated NPM1. Here, we went on to confirm the important role of FOXM1 in increased chemoresistance in AML. A multiinstitution retrospective study was conducted to link FOXM1 expression to clinical outcomes in AML. We establish nuclear FOXM1 as an independent clinical predictor of chemotherapeutic resistance in intermediate-risk AML in a multivariate analysis incorporating standard clinicopathologic risk factors. Using colony assays, we show a dramatic decrease in colony size and numbers in AML cell lines with knockdown of FOXM1, suggesting an important role for FOXM1 in the clonogenic activity of AML cells. In order to further prove a potential role for FOXM1 in AML chemoresistance, we induced an FLT3-ITD-driven myeloid neoplasm in a FOXM1-overexpressing transgenic mouse model and demonstrated significantly higher residual disease after standard chemotherapy. This suggests that constitutive overexpression of FOXM1 in this model induces chemoresistance. Finally, we performed proof-of-principle experiments using a currently approved proteasome inhibitor, ixazomib, to target FOXM1 and demonstrated a therapeutic response in AML patient samples and animal models of AML that correlates with the suppression of FOXM1 and its transcriptional targets. Addition of low doses of ixazomib increases sensitization of AML cells to chemotherapy backbone drugs cytarabine and the hypomethylator 5-azacitidine. Our results underscore the importance of FOXM1 in AML progression and treatment, and they suggest that targeting it may have therapeutic benefit in combination with standard AML therapies.

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