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Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally. Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes.
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Metilação de DNA , MicroRNAs , Suínos/genética , Animais , Epigênese Genética , MicroRNAs/genética , DNA , Desenvolvimento Muscular/genéticaRESUMO
The COVID-19 global pandemic has had severe, unpredictable and synchronous impacts on all levels of perishable food supply chains (PFSC), across multiple sectors and spatial scales. Aquaculture plays a vital and rapidly expanding role in food security, in some cases overtaking wild caught fisheries in the production of high-quality animal protein in this PFSC. We performed a rapid global assessment to evaluate the effects of the COVID-19 pandemic and related emerging control measures on the aquaculture supply chain. Socio-economic effects of the pandemic were analysed by surveying the perceptions of stakeholders, who were asked to describe potential supply-side disruption, vulnerabilities and resilience patterns along the production pipeline with four main supply chain components: a) hatchery, b) production/processing, c) distribution/logistics and d) market. We also assessed different farming strategies, comparing land- vs. sea-based systems; extensive vs. intensive methods; and with and without integrated multi-trophic aquaculture, IMTA. In addition to evaluating levels and sources of economic distress, interviewees were asked to identify mitigation solutions adopted at local / internal (i.e., farm-site) scales, and to express their preference on national / external scale mitigation measures among a set of a priori options. Survey responses identified the potential causes of disruption, ripple effects, sources of food insecurity, and socio-economic conflicts. They also pointed to various levels of mitigation strategies. The collated evidence represents a first baseline useful to address future disaster-driven responses, to reinforce the resilience of the sector and to facilitate the design reconstruction plans and mitigation measures, such as financial aid strategies.
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BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Náusea/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Vômito/diagnóstico , Adulto , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
OBJECTIVE: Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to "platinum-sensitive" and "-resistant" recurrences according to platinum-free interval. METHODS: This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. RESULTS: Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7â¯m vs 9.7â¯m, pâ¯=â¯0.7) and overall survival (OS) (23.9â¯m vs 24.8â¯m, pâ¯=â¯0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6â¯m vs 3.6â¯m, pâ¯=â¯0.03) and OS (41.9â¯m vs 9.5â¯m pâ¯=â¯0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (pâ¯=â¯0.91) and OS (pâ¯=â¯0.25) differences between platinum-sensitive and -resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (pâ¯=â¯0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. CONCLUSION: Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.
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Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Topotecan/administração & dosagem , Adulto JovemRESUMO
The endometrial cancer (EC)-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-EN24), was developed and validated in one study. We independently validated and assessed the psychometric properties of the instrument. Two hundred and eight women with EC before surgery, during adjuvant treatment and follow-up; in three different cancer centres completed the EORTC QLQ-C30 and the EN24. The questionnaire's completion rate was 100%, except sexuality items, that were answered by 35% of patients. All item-scale correlations for the multi-item scales exceeded the .4 criterion and correlated well with their own scale, while correlations with the other scales were low. The internal consistency of all multi-item scales were satisfactory (Cronbach's alpha coefficients ranging from .77 to .97). Discriminance for single-item scales was low. The QLQ-EN24 module discriminated well between clinically different patients, and there were no differences in quality of life questionnaire scales between patients with body mass index ≤30 when compared to those with >30. This validation study supports the reliability, as well as convergent and divergent validity of the EORTC QLQ-EN24. The module is a useful instrument for the assessment of QOL in patients with EC. However, data concerning sexuality should be interpreted with caution.
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Neoplasias do Endométrio/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/normas , PsicometriaRESUMO
Carcinoma of the recto-vaginal septum is an extremely rare entity. We performed a MEDLINE-based search on recto-vaginal septum carcinoma, focussing on its management, in order to clarify which are the best treatment options for this disease. In addition an unpublished case report has been added to the review. 34 case reports were included in our review. Surgery and adjuvant chemoradiation therapy seem to be the most common treatment option. However, since primary surgical treatment leads to mutilation by removing a large portion of the vagina and the anal sphincter with a permanent terminal colostomy, primary platinum-based chemoradiation therapy could be considered. In case of extragastrointestinal stromal tumours primary surgical treatment seems to be the best option. Due to the rarity of this entity only limited data is available. Therefore further investigation is necessary.
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Carcinoma/terapia , Neoplasias Retais/terapia , Neoplasias Vaginais/terapia , Adulto , Canal Anal/cirurgia , Carcinoma/patologia , Quimiorradioterapia Adjuvante/métodos , Terapia Combinada , Feminino , Humanos , Neoplasias Retais/patologia , Vagina/cirurgia , Neoplasias Vaginais/patologiaRESUMO
BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.
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Educação Médica Continuada , Oncologia , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Oncologia/educação , Neoplasias/terapia , Cuidados Paliativos , Inquéritos e Questionários , Recursos HumanosRESUMO
INTRODUCTION: High mortality rate, absence of reliable methods for early diagnosis and poor prognosis of advanced ovarian cancer prompted to investigate the role of prophylactic oophorectomy in BRCA1 mutation carriers as well as evaluate the expression of BRCA1, p53, Nm23, and KAI1 proteins in ovarian tissue from these patients. MATERIALS AND METHODS: Ovaries from BRCA1 mutation carriers underwent prophylactic adnexectomy and control group of patients were operated from other than cancer reasons. The expression of selected proteins was studied using immunohistochemical staining. The intensity of immunostaining and the number of tumor cells showing the reaction for selected proteins were analyzed. RESULTS: We have analyzed ovarian tissues from 18 BRCA1 mutation carriers and 11 women included in control group. Positive expression of BRCA1 protein was presented in 83.3 % cases in BRCA1 mutation carriers and in 72.7 % in the control group (p > 0.05). Positive expression of p53 protein was observed, respectively, in 27.8 vs. 36.4 % (p > 0.05), Nm23 protein 77.7 vs. 90.9 % (p > 0.05), and KAI1 in 72.2 vs. 72.7 % (p > 0.05). Mean percent of tumor cells that showed the reaction for selected proteins as well as the intensity of immunostaining for all analyzed proteins seems to be lower in BRCA1 mutation carriers. CONCLUSIONS: However, any significant differences between study group and control group have not been found; there were similar trends showing reduced expression of studied proteins in BRCA1 mutation carriers.
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Biomarcadores Tumorais/metabolismo , Síndrome Hereditária de Câncer de Mama e Ovário/prevenção & controle , Ovariectomia , Ovário/metabolismo , Salpingectomia , Adulto , Proteína BRCA1/metabolismo , Estudos de Casos e Controles , Feminino , Genes BRCA1 , Predisposição Genética para Doença , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/metabolismo , Humanos , Imuno-Histoquímica , Proteína Kangai-1/metabolismo , Pessoa de Meia-Idade , Mutação , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Ovário/cirurgia , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Treatment of advanced-stage ovarian carcinoma includes radical cytoreductive surgery, which aims at removing all visible tumor tissue followed by platinum and paclitaxel chemotherapy. Complete tumor resection may require extended surgical procedures. This paper reports on the prognostic impact of extensive surgery and surgical morbidity in patients with advanced-stage ovarian carcinoma. METHODS: Patients with ovarian carcinoma [Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIB-IV] undergoing primary surgery in our tertiary gynecologic oncology unit between 1997 and 2007 were eligible for this study. The impact of established prognostic factors and the interaction with extent of surgical procedures on survival were assessed. RESULTS: A total of 267 patients aged between 29 and 88 years (median 64 years) were eligible for this study. Overall survival time was improved in patients who underwent complete tumor resection [hazard ratio (HR) 3.61 (1.91-6.61), P < 0.001]. No significant survival difference was observed between completely operated patients in whom extended or standard surgical procedures were applied [HR 1.37 (0.70-2.69), P = 0.358], and severe surgical complications were found to be equally distributed between the two patient groups. CONCLUSIONS: Our results may encourage the application of extended surgical procedures in patients who would otherwise be rendered incompletely debulked after primary cytoreduction. We could demonstrate an impact of complete tumor resection on patient prognosis and this was not traded off for extensive additional surgical morbidity.
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Neoplasias Ovarianas/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Anions of many types, both organic and inorganic, farmiliar and exotic, can be generated in the gas phase by rational chemical synthesis in a flowing afterglow apparatus. Once formed, the rates, products, and mechanisms of their reactions with neutral species of all kinds can be studied, not only at room temperature but at higher energies in a drift field. These completely unsolvated ions undergo a large number of reactions that are analogous to those they undergo in solution, as well as some that are less familiar. New types of ions, for which there are no counterparts in solution, can be produced and their chemical reactions explored.
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Evidence is rapidly accumulating that links cigarette smoke (CS) exposure in utero with the development of a variety of disease pathologies in the older offspring including, type 2 diabetes, obesity, certain childhood cancers and respiratory disorders. The role that the fetal environment plays in these late-onset outcomes and the underlying cellular/molecular mechanisms by which these CS-induced effects may occur are currently unknown. Although we are becoming more aware of the fact that prenatal insult can underlie childhood/adult diseases, critical knowledge gaps still exist including gene-environment interactions, and how a CS-induced imbalance in immune dynamics (i.e. TH1/TH2) might affect asthma development and/or exacerbation later in life. In this mini-review we introduce the concept of sexual dimorphism in CS-induced late-onset disease outcomes, as well as explore the mechanisms by which CS exposure in utero can lead to cardiovascular, cancer and respiratory abnormalities in the exposed offspring. By addressing such questions using animal models, appropriate intervention strategies can be developed that will help to protect children's health and their long-term quality of life.
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Doenças Cardiovasculares/etiologia , Neoplasias/etiologia , Efeitos Tardios da Exposição Pré-Natal , Doenças Respiratórias/etiologia , Fumar/efeitos adversos , Animais , Doença Crônica , Feminino , Predisposição Genética para Doença , Humanos , Modelos Animais , Gravidez , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Marine harbours are the focus of a diverse range of activities and subject to multiple anthropogenically induced pressures. Support for environmental management options aimed at improving degraded harbours depends on understanding the factors which influence people's perceptions of harbour environments. We used an online survey, across 12 harbours, to assess sources of variation people's perceptions of harbour health and ecological engineering. We tested the hypotheses: 1) people living near impacted harbours would consider their environment to be more unhealthy and degraded, be more concerned about the environment and supportive of and willing to pay for ecological engineering relative to those living by less impacted harbours, and 2) people with greater connectedness to the harbour would be more concerned about and have greater perceived knowledge of the environment, and be more supportive of, knowledgeable about and willing to pay for ecological engineering, than those with less connectedness. Across twelve locations, the levels of degradation and modification by artificial structures were lower and the concern and knowledge about the environment and ecological engineering were greater in the six Australasian and American than the six European and Asian harbours surveyed. We found that people's perception of harbours as healthy or degraded, but not their concern for the environment, reflected the degree to which harbours were impacted. There was a positive relationship between the percentage of shoreline modified and the extent of support for and people's willingness to pay indirect costs for ecological engineering. At the individual level, measures of connectedness to the harbour environment were good predictors of concern for and perceived knowledge about the environment but not support for and perceived knowledge about ecological engineering. To make informed decisions, it is important that people are empowered with sufficient knowledge of the environmental issues facing their harbour and ecological engineering options.
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A considerable number of biochemical and physiologic studies evaluate the roles of gonadotropins in carcinogenesis. Latest reports show that human chorionic gonadotropin (hCG), and especially its beta subunit, are secreted by a variety of malignant tumors of different origin. However, the mechanism of hCG action and its role in tumor development is not known yet. This study, with the help of reverse transcription-polymerase chain reaction and immunohistochemistry, is an attempt to document the molecular presence of the hCGbeta and luteinizing hormone/hCG receptor (LH/hCGR) in the ovarian, endometrial, and uterine cervix cancer tissues. The LH/hCGR, coexpressed with hCGbeta, may act as a potential mediator of hCG action in nontrophoblastic gynecological cancers.
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Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/metabolismo , Receptores do LH/metabolismo , Neoplasias Uterinas/metabolismo , Gonadotropina Coriônica Humana Subunidade beta/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores do LH/genética , Neoplasias Trofoblásticas/genética , Neoplasias Trofoblásticas/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologiaRESUMO
AIM: Amino acid PET has become an important diagnostic tool for brain tumour imaging. In this data analysis, the potential impact of amino acid PET with 3-O-methyl-6-[(18)F]fluoro-L-DOPA ([(18)F]OMFD) on radiation treatment planning is addressed by the following questions: 1. Was tumour tissue identified with OMFD-PET which was not covered by the conventionally derived planning target volume (PTV)? 2. Would the PTV have been changed incorporating OMFD-PET? PATIENTS, METHODS: OMFD-PET of 25 patients after subtotal resection of malignant glioma was evaluated. The region of elevated tracer uptake of PET and of contrast enhancing masses on MRI were outlined as separate gross tumour volumes (GTV(MRI) and GTV(OMFD)) and reconstructed in the planning CT for comparison with the conventionally drawn GTV(conv). A PTV(new) based on GTV(conv+MRI) was calculated. Pairwise differential volumes were calculated to estimate overlap and differential volumes delineation by each image modality and the PTV(conv) and PTV(new) respectively. RESULTS: Differential volume analysis showed > 10 cm(3) of GTV(OMFD) outside GTV(conv) and GTV(MRI) in 5/25 patients respectively. From GTV(MRI) > 10 cm(3) were found outside GTV(OMFD) in 8/25 patients. Although all tumour areas indicated by [(18)F]OMFD were covered by the conventionally derived PTV, based on a GTV(OMFD+MRI), the PTV(new) would have been enlarged >20% in seven patients. In seven patients the PTV(new) would have been reduced. CONCLUSION: OMFD-PET indicated tumour tissue outside the tumour region identified with MRI, adding valuable information for the delineation of the GTV in radiation treatment planning. OMFD-PET contains the potential to tailor the high dose radiation to the appropriate tumour volume, especially if dose escalation is desired.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Di-Hidroxifenilalanina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Biópsia , Neoplasias Encefálicas/patologia , Feminino , Radioisótopos de Flúor , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The aim of the study was to evaluate hypoxia markers (VEGF, GLUT-1, and HIF-1alpha) in cervical cancer tissue depending on staging (FIGO) and grading. We also analyzed the adverse effects of radiotherapy according to expression levels of hypoxic markers in the studied tissue. MATERIAL AND METHODS: Expression of hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF, also known as proangiogenic factor) were estimated in biopsy or surgical specimens from 106 patients diagnosed with uterine cervical cancer. Immunohistochemical methods with EbVision+ complex using monoclonal antibodies anti-VEGF and anti-HIF-1alpha and polyclonal antibody anti-GLUT-1 were applied. RESULTS AND CONCLUSIONS: Hypoxia features measured by percentage of cells undergoing reaction with antibodies anti-HIF-1alpha, anti-GLUT-1 and anti-VEGF were similar in all clinical stages; however the biggest hypoxia features were shown in low differentiated cancers G2 and G3. The 5-year survival for FIGO Stage III patients was shorter in cases with a high expression of hypoxic markers. We observed adverse effects in 45.3% of patients, which occurred more often in patients with higher expression of the studied factors. The presence of hypoxic cells is established as one of the most important factors affecting resistance against tumor radiotherapy and patient prognosis.
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Hipóxia Celular , Transportador de Glucose Tipo 1/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Neoplasias do Colo do Útero/patologia , Fator A de Crescimento do Endotélio Vascular/análise , Biomarcadores/análise , Feminino , Humanos , Prognóstico , Análise de Sobrevida , Neoplasias do Colo do Útero/metabolismoRESUMO
Cytoreductive surgery is the backbone of the multimodal therapy in primary ovarian cancer patients. Despite the effect of various tumor biological factors such as grading and histological subtype, the surgical outcome is the most important prognostic factor for both progression free- and overall survival. In contrast, the management of recurrent situation has long remained a subject of an emotional international discussion. To date, only few prospective studies have focused on the effect of surgery in relapsed ovarian cancer. The available retrospective data associate complete cytoreduction with prognosis improvement. However, the selection of patients eligible for surgery in recurrent situation is the essential issue. The establishment of predictive factors for complete tumor resection and defining the patient group with recurrent disease who might profit from this approach are crucial. The available predictors of complete resection depend on the results of primary surgery and the current patient's situation. Women who underwent primary complete cytoreduction are in good performance status, and those who have only minimal ascites volume (less than 500 ml) in the recurrent situation have 76% likelihood of undergoing complete resection and survival prolongation. Moreover, the complete cytoreduction in the tertiary cytoreductive approach has been evaluated and showed a potential positive influence on patients' survival. This review concentrates on the recent data and highlights the need of further randomized trials to develop and incorporate operative standards in recurrent ovarian cancer.
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Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Antineoplásicos/uso terapêutico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups.
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Bupropiona/uso terapêutico , Naltrexona/uso terapêutico , Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Cooperação do Paciente , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Epithelial ovarian cancer is a highly fatal gynecologic malignancy with a poor prognosis. Therefore, identification of new modifiable prognostic factors is important. Due to the fact that the effect of body weight changes during chemotherapy for EOC is still not very well known we aimed to describe, considering evidence, role of body weight changes in relation to survival. MATERIALS AND METHODS: Between October 2014 and August 2015 we systematically searched the following databases: Medline, Scopus, Web of Science and EMBASE to identify the studies describing the influence of body weight changes on survival in patients undergoing chemotherapy for EOC. RESULTS: We identified 601 potentially relevant publications, however finally only one article was included for data extraction and analysis. The overall survival in the selected paper was significantly associated with body weight changes during the first-line chemotherapy. Nevertheless, no influence on progression free survival was found. CONCLUSIONS: The analyzed data provides initial evidence, showing poorer overall survival associated with body weight loss and improved overall survival associated with body weight gain during primary chemotherapy for epithelial ovarian cancer. Prospective and retrospective trials are an urgent calling to confirm this conclusion.
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Peso Corporal , Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/fisiopatologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Cytoreductive surgery remains an accepted standard treatment of primary ovarian cancer. In advanced stages adjuvant platin/taxane chemotherapy with addition of anti-angiogenic agent, i.e., bevacizumab is recommended. The management of recurrent ovarian cancer remains a field of controversies. Surgery and/or systemic treatment are currently investigated in prospective trials. Retrospective data show prognosis improvement in patients who underwent complete cytoreduction. Thus, the selection of patients eligible for surgery in recurrent situation is the essential issue. The available predictors of complete resection depend on results of primary surgery and current patients situation. Women who fulfill these criteria have 76% likelihood of undergoing complete resection and survival prolongation. On the other hand there is a large group of patients in whom surgery might be too dangerous and demand an effective systemic treatment. Currently in a second-line several options are available, again including anti-angiogenic agents. The management of further recurrences is a subject of several clinical trials, nevertheless standards are still missing. Due to histological subtype and/or BRCA mutation status, the therapy in ovarian cancer might undergo revision in a near future.
Assuntos
Neoplasias Ovarianas/terapia , Feminino , Previsões , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologiaRESUMO
Chicken repeat 1 (CR1) elements comprise a family of non-long terminal repeat (LTR) retrotransposons that have several noteworthy features. For example, whereas most other non-LTR elements have poly(A) tracts or other simple A-rich repeats at their 3' ends, the 3' ends of CR1 elements conform to the consensus [(CATTCTRT)(GATTCTRT)1-3]. CR1 elements also display an unusual bias for severe 5' truncations: only approx. 30 (out of a total of approx. 30 000) CR1 elements in the chicken genome include significant portions of the pol-like open reading frame (ORF) that we previously identified and partially sequenced [Burch et al. (1993) Proc. Natl. Acad. Sci. USA 90, 8199-8203]. In the present study we derived a consensus sequence for this entire ORF (ORF2) as well as an upstream ORF (ORF1) and part of a 5' untranslated region (UTR). The conceptual translation product of ORF2 is predicted to contain an endonuclease domain in addition to a reverse transcriptase domain. These results suggest that CR1 elements retrotranspose using a "nick and prime" mechanism similar (but not identical) to other families of non-LTR elements.