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1.
Proc Biol Sci ; 291(2018): 20232867, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38471562

RESUMO

A delayed foveal mask affects perception of peripheral stimuli. The effect is determined by the timing of the mask and by the similarity with the peripheral stimulus. A congruent mask enhances performance, while an incongruent one impairs it. It is hypothesized that foveal masks disrupt a feedback mechanism reaching the foveal cortex. This mechanism could be part of a broader circuit associated with mental imagery, but this hypothesis has not as yet been tested. We investigated the link between mental imagery and foveal feedback. We tested the relationship between performance fluctuations caused by the foveal mask-measured in terms of discriminability (d') and criterion (C)-and the scores from two questionnaires designed to assess mental imagery vividness (VVIQ) and another exploring object imagery, spatial imagery and verbal cognitive styles (OSIVQ). Contrary to our hypotheses, no significant correlations were found between VVIQ and the mask's impact on d' and C. Neither the object nor spatial subscales of OSIVQ correlated with the mask's impact. In conclusion, our findings do not substantiate the existence of a link between foveal feedback and mental imagery. Further investigation is needed to determine whether mask interference might occur with more implicit measures of imagery.


Assuntos
Imaginação , Percepção Visual , Fóvea Central , Inquéritos e Questionários , Personalidade
2.
Br J Surg ; 111(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38593043

RESUMO

BACKGROUND: Health state utility values provide the quality component of quality-adjusted life years and are essential for health economic analyses, such as the National Institute for Health and Care Excellence Technology Appraisal. The aims of this systematic review were to: catalogue utility values for health states experienced by patients with hand conditions; provide pooled utility estimates for common hand conditions; and determine how utilities have been estimated. METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted (registered in PROSPERO, the international prospective register of systematic reviews (CRD42021226098)). Five databases were searched from inception until April 2023 (Embase, MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL)). All studies that reported primary utility values for hand health states in adult patients were eligible for inclusion. Pooled utility estimates were determined across conditions and intervention status using random-effects meta-analysis. RESULTS: A total of 10 254 articles were identified; 57 studies met the full inclusion criteria and reported 363 distinct health state utility values. Health state utility values were estimated using a range of methods; the most common measure was the EQ-5D. Pooled utility estimates for carpal tunnel syndrome and hand osteoarthritis before surgical intervention were 0.69 (95% c.i. 0.66 to 0.73) and 0.63 (95% c.i. 0.60 to 0.67) respectively. CONCLUSION: Pooled utility estimates for patients with untreated carpal tunnel syndrome and hand osteoarthritis are 11% and 18% lower than age-matched population norms respectively. Hand conditions have a significant detrimental impact on health-related quality of life and this study provides catalogued utility values for use in future economic analyses to support the delivery of value-based hand surgery.


Assuntos
Síndrome do Túnel Carpal , Osteoartrite , Adulto , Humanos , Qualidade de Vida , Síndrome do Túnel Carpal/cirurgia
3.
Int J Gynecol Cancer ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858105

RESUMO

OBJECTIVES: Despite the individualized starting dose for maintenance therapy in ovarian cancer, the niraparib dose reduction rate remains high. The aim of this study was to evaluate the impact of niraparib dose reduction on progression-free survival in newly diagnosed primary advanced ovarian cancer and recurrent ovarian cancer patients. We also aimed to compare the reduction rates and the safety of niraparib on primary and relapse groups, and identify which factors may predict dose reduction. METHODS: Patients with primary or recurrent ovarian cancer in maintenance who received niraparib between 2019 and 2022 were retrospectively evaluated. Niraparib dosing was based on individualized starting dose of 300 or 200 mg/day. The impact of niraparib dose reductions was focused on patients treated with 200 or 100 mg in both groups. Reduction rates, adverse events and predictive factors of reduction were assessed in each study group. The primary endpoint was progression-free survival in primary and relapse groups; the secondary endpoints were the reduction rates, the safety and tolerability of niraparib in both groups. RESULTS: Of 215 patients identified, 124 (57.7%) primary and 91 (42.3%) recurrent ovarian cancer patients were included. The majority of patients started niraparib at 200 mg/day (92.7% primary and 80.2% relapse group); dose reductions from 300 or 200 mg/day to 200 or 100 mg/day occurred more frequently within cycles 1-3 (67% primary and 45% relapse group, p=0.001). Grade≥3 adverse events were lower in the relapse group (54.8% primary and 35.1% relapse, p=0.001). In both groups, dose modifications over the treatment did not significantly impair median progression-free survival. Univariate and multivariate analysis demonstrated that weight and platinum-doublets were possible risk factors for dose reduction. CONCLUSIONS: Niraparib dose reduction occurs in almost half of patients within cycles 1-3, although it is significantly more common in the first-line setting. Survival outcomes seem not to be impaired by dose reduction.

4.
Int J Gynecol Cancer ; 34(1): 88-98, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38805344

RESUMO

OBJECTIVE: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases. METHODS: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases. RESULTS: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line. CONCLUSIONS: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.


Assuntos
Neoplasias Encefálicas , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/mortalidade , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/secundário , Carcinoma Epitelial do Ovário/patologia , Idoso , Adulto , Proteína BRCA2/genética , Proteína BRCA1/genética
5.
Lett Appl Microbiol ; 77(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38658187

RESUMO

Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.


Assuntos
Antifúngicos , Candida parapsilosis , Candidemia , Proteínas de Choque Térmico HSP90 , Micafungina , Humanos , Recém-Nascido , Antifúngicos/farmacologia , Benzoquinonas/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Candida parapsilosis/genética , Candidemia/microbiologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Equinocandinas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Lactamas Macrocíclicas/farmacologia , Lipopeptídeos/farmacologia , Micafungina/farmacologia , Testes de Sensibilidade Microbiana
6.
Eur Respir J ; 62(4)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37678955

RESUMO

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting ß2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.


Assuntos
Antiasmáticos , Asma , Adulto , Adolescente , Humanos , Fumarato de Formoterol/uso terapêutico , Asma/tratamento farmacológico , Asma/induzido quimicamente , Corticosteroides , Administração por Inalação , Budesonida
7.
Int J Gynecol Cancer ; 33(2): 257-262, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36581488

RESUMO

OBJECTIVE: To evaluate the role of different specific types of germline breast cancer susceptibility BRCA mutations on the age of onset of high grade serous ovarian cancer. METHODS: This was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations in BRCA1/2 genes, treated between January 2011 and December 2020 in three academic centers in Europe. Patients were classified into four groups related to the type of BRCA1/2 genes mutation: frameshift, missense, nonsense, and splicing. Data from patients with splicing mutations were removed from the analysis because of the small numbers. The other three groups were compared. RESULTS: Excluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. The BRCA1 gene was affected in 324 (68.4%) cases, while BRCA2 was involved in 150 (31.6%) women (p=0.06). We found a difference of more than 5 years in the age of onset of high grade serous ovarian cancer between BRCA1 and BRCA2 patients (mean 53.3 years vs 58.4 years; p=0.001), with a mean age of 55.1 years. Patients with nonsense germline mutations had the youngest age of onset, while women with frameshift mutations had the oldest age of onset of high grade serous ovarian cancer (mean 52.2 years vs mean 55.9 years), both in the BRCA1 and BRCA2 subgroups. There was no statistically significant difference in age of onset between early and advanced groups (mean 55.8 years vs 55.0 years; p=0.55). CONCLUSION: Different types of germline BRCA mutations could determine different ages for onset of high grade serous ovarian cancer. If confirmed in larger series, this finding might have a clinical impact, potentially leading to a more tailored approach for risk reducing surgery for the prevention of high grade serous ovarian cancer.


Assuntos
Proteína BRCA2 , Neoplasias Ovarianas , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteína BRCA1/genética , Proteína BRCA2/genética , Genes BRCA2 , Mutação em Linhagem Germinativa , Mutação , Neoplasias Ovarianas/genética , Estudos Retrospectivos
8.
Semin Cancer Biol ; 77: 144-166, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34464704

RESUMO

Ovarian cancer (OC) remains a fatal malignancy because most patients experience recurrent disease, which is resistant to chemotherapy. The outcomes for patients with platinum-resistant OC are poor, response rates to further chemotherapy are low and median survival is lower than 12 months. The complexity of platinum-resistant OC, which comprises a heterogeneous spectrum of diseases, is indeed far from being completely understood. Therefore, comprehending tumors' biological behaviour to identify reliable biomarkers, which may predict responses to therapies, is a demanding challenge to improve OC management. In the age of precision medicine, efforts to overcome platinum resistance in OC represent a dynamic and vast field in which innovative drugs and clinical trials rapidly develop. This review will present the exceptional biochemical environment implicated in OC and highlights mechanisms of chemoresistance. Furthermore, innovative molecules and new therapeutic opportunities are presented, along with currently available therapies and ongoing clinical trials.


Assuntos
Biomarcadores Tumorais , Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos , Animais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos
9.
Br J Clin Pharmacol ; 87(7): 2807-2817, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33269485

RESUMO

AIMS: Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle-aged people with diabetes. METHODS: A repeated cross-sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012-2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria for 45-64 years old. Chi-square tests and regression analysis were applied. RESULTS: The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45-54 years, 50.3% in those aged 55-64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle-aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long-term high-dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. CONCLUSIONS: Polypharmacy increased in older and middle-aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle-aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age.


Assuntos
Diabetes Mellitus , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Estudos Transversais , Humanos , Prescrição Inadequada , Pessoa de Meia-Idade , Polimedicação , Prevalência
10.
Curr Oncol Rep ; 23(6): 64, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33855620

RESUMO

PURPOSE OF REVIEW: This study aims to assess the current state of cardio-oncology in reference to advocacy efforts, access to care, and perspective of stakeholders in their ability to provide patient care as well as development of "across the aisle" synergy among cardiologists and oncologists and academic and non-academic centers in various worldwide locations. RECENT FINDINGS: During the last decade, there has been a significant and diverse growth in cardio-oncology. We reviewed the experience from cardiologists and oncologists across different healthcare systems, the global trends, the role of collaborative networks, and the importance of advocacy efforts. Cardio-oncology will continue to grow, but there is an unmet need to increase awareness, improve education, and expand access to care to larger segments of the cancer population in order to have a more significant impact on their health. The growing collaboration through professional societies and collaborative networks provides an opportunity to advance the cardiovascular care of cancer patients to meet the projected needs in a growing and more diverse population.


Assuntos
Cardiologia , Colaboração Intersetorial , Oncologia , Cardiologia/economia , Cardiologia/educação , Doenças Cardiovasculares/complicações , Acessibilidade aos Serviços de Saúde , Humanos , Oncologia/economia , Oncologia/educação , Neoplasias/complicações , Defesa do Paciente , Mídias Sociais
11.
Clin Oral Investig ; 25(4): 1767-1774, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32748074

RESUMO

OBJECTIVE: To investigate the efficacy of sclerotherapy with monoethanolamine oleate (MEO) in a series of cases of benign oral vascular lesions (BOVL). MATERIAL AND METHODS: Clinical records and images were retrieved (2015-2019), and data regarding age, gender, location, size, symptomatology, treatment and outcomes of patients were collected. All patients were diagnosed according to the classification of International Society for the Study of Vascular Anomalies and received the same treatment protocol (MEO 0.05 g/mL). The collected data were submitted to descriptive analysis and Pearson's chi-square test (p ≤ 0.05). RESULTS: Thirty-seven patients were treated. Most were female (70.3%) aged 9 to 88 years (median, 57.5 ± 17.4 years). Lower lip (54.1%) was the most affected site followed by buccal mucosa (16.2%). Thirty-two lesions were asymptomatic and 35.1% showed ≤ 0.5 cm in size. In 48.6% of the patients, only one application of MEO was performed. Complete regression occurred in 62.2% of cases, whereas 27% showed partial regression. One patient showed hypersensitivity during treatment. There was no significant difference between clinical outcome and age, anatomic site, size, and number of applications of MEO. CONCLUSIONS: Sclerotherapy with MEO is an acceptable and affordable treatment and can provide satisfactory results in BOVL, especially where other treatment options could compromise the esthetic aspects. CLINICAL RELEVANCE: As it is a non-invasive therapy leading, in most cases, to adequate clinical results, safety, and tolerability, sclerotherapy with MEO can be considered an effective treatment for BOVL.


Assuntos
Escleroterapia , Malformações Vasculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estética Dentária , Feminino , Humanos , Pessoa de Meia-Idade , Ácidos Oleicos , Soluções Esclerosantes/uso terapêutico , Resultado do Tratamento , Malformações Vasculares/tratamento farmacológico , Adulto Jovem
12.
Int J Mol Sci ; 22(24)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34948446

RESUMO

Ovarian cancer (OC) is the second most common cause of death in women with gynecological cancer. Considering the poor prognosis, particularly in the case of platinum-resistant (PtR) disease, a huge effort was made to define new biomarkers able to help physicians in approaching and treating these challenging patients. Currently, most data can be obtained from tumor biopsy samples, but this is not always available and implies a surgical procedure. On the other hand, circulating biomarkers are detected with non-invasive methods, although this might require expensive techniques. Given the fervent hope in their value, here we focused on the most studied circulating biomarkers that could play a role in PtR OC.


Assuntos
Biomarcadores Tumorais/sangue , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/sangue , Platina/uso terapêutico , Prognóstico
13.
Pract Neurol ; 21(5): 427-430, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34050003

RESUMO

Cerebral radiation necrosis is the most serious late reaction to high doses of ionising radiation to the brain, and its treatment is generally unsatisfactory. We present a patient who developed cerebral radiation necrosis after protracted fluoroscopy during repeated embolisations of an extracranial arteriovenous malformation. Treatment with bevacizumab (a humanised murine monoclonal antibody against vascular endothelial growth factor) was followed by neurological and radiological improvements.


Assuntos
Lesões por Radiação , Fator A de Crescimento do Endotélio Vascular , Animais , Bevacizumab/efeitos adversos , Humanos , Doença Iatrogênica , Camundongos , Necrose/etiologia , Lesões por Radiação/complicações
14.
Heart Fail Rev ; 24(6): 833-846, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31197563

RESUMO

Takotsubo syndrome is a disease of great clinical importance that remains underdiagnosed. It is a form of acute heart failure characterized by a transient wall motion abnormality of the left ventricular apex typically triggered by emotional or physical stress. Takotsubo syndrome is commonly associated with cancer and results in poor outcomes. Therefore, early recognition and prompt therapy are essential to improve prognosis. The aim of this manuscript is to review the consequences of the association between cancer and Takotsubo to summarize the available evidence to guide physicians to improve the management of these patients.


Assuntos
Ventrículos do Coração/fisiopatologia , Neoplasias/complicações , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/fisiopatologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Prevalência , Prognóstico , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Volume Sistólico/fisiologia , Cardiomiopatia de Takotsubo/mortalidade , Cardiomiopatia de Takotsubo/terapia , Remodelação Ventricular/fisiologia , Adulto Jovem
15.
Oncology ; 97(5): 306-310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437848

RESUMO

BACKGROUND: Chemotherapy at the end of life is a complex and challenging problem in medical oncology. Patients affected by ovarian cancer (OC) often experience a chronicization and slow progression of their disease, and chemotherapy is proposed until the end of life. METHODS: We retrospectively analyzed data from patients affected by OC treated at our department and having died in the period between 2007 and 2017 and evaluated the frequency of antineoplastic treatments until the end of life, the chemotherapy-related toxicity, mortality, and the most frequent palliative care measure adopted. RESULTS: A total of 110 OC deaths, after a median overall patient survival of 52.8 months (range 4-232), were analyzed. 77.3% of the patients presented with FIGO stage IIIC OC at diagnosis and 12.7% with FIGO stage IV OC. 89% of the histological types were serous papillary. The median age was 55 years (range 31-82) at diagnosis and 60 years (range 33-84) at death. Of the 110 patients analyzed, 85 (77%) had undergone chemotherapy over the last 3 months of life and 38% had chemotherapy even during the last month of life. The overwhelming majority of patients (81%) needed supportive therapies. Despite the treatments received, the majority of the patients died at home, 19% died in hospital, and only 4.5% died in hospice. The quality of life of these patients decreased dramatically in the last 30 days, but best supportive care improved the symptoms. CONCLUSIONS: End-of-life chemotherapy for OC patients is a thorny problem. More studies and a multidisciplinary approach are needed to better treat these patients.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Assistência Terminal , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/psicologia , Qualidade de Vida , Estudos Retrospectivos
16.
Immunology ; 151(2): 154-166, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28140444

RESUMO

Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3-/- , ASC-/- and caspase-1-/- . All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1ß, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.


Assuntos
Inflamassomos/imunologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sporothrix/imunologia , Esporotricose/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Sporothrix/citologia , Esporotricose/microbiologia
17.
Neuroendocrinology ; 104(2): 183-193, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27161333

RESUMO

BACKGROUND/AIMS: Although craniopharyngioma (CP) is histologically benign, it is a pituitary tumour that grows rapidly and often recurs. Adamantinomatous CP (ACP) was associated with an activating mutation in ß-catenin, and it has been postulated that pituitary stem cells might play a role in oncogenesis in human ACP. Stem cells have also been identified in pituitary adenoma. Our aim was to characterize the expression pattern of ABCG2, CD44, DLL4, NANOG, NOTCH2, POU5F1/OCT4, SOX2, and SOX9 stem cell markers in human ACP and pituitary adenoma. METHODS AND RESULTS: We studied 33 patients (9 ACP and 24 adenoma) using real-time quantitative PCR (RT-qPCR) and immunohistochemistry. SOX9 was up-regulated in ACP, exhibiting positive immunostaining in the epithelium and stroma, with the highest expression in patients with recurrence. CD44 was overexpressed in ACP as confirmed by immunohistochemistry. SOX2 did not significantly differ among the tumour types. The RT-qPCR array showed an increased expression of MKI67,OCT4/POU5F1, and DLL4 in all tumours. NANOG was decreased in ACP. ABCG2 was down-regulated in most of the tumours. NOTCH2 was significantly decreased in the adenomas. CONCLUSION: Our results confirm the presence of stem cell markers in human pituitary tumours as well as the different expression patterns of ACP and adenoma. These findings suggest that ACP may originate from a more undifferentiated cell cluster. Additionally, SOX9 immunodetection in the stroma and the highest expression levels related to the relapse of patients suggest a contribution to the aggressive behaviour and high recurrence of this tumour type.


Assuntos
Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Craniofaringioma/metabolismo , Células-Tronco Neurais/metabolismo , Neoplasias Hipofisárias/metabolismo , Adenoma/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Craniofaringioma/patologia , Feminino , Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Adulto Jovem
18.
Mol Cell Biochem ; 415(1-2): 119-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27015684

RESUMO

During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca(2+)] i was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.


Assuntos
Caspases/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Melanoma/patologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Proteínas e Peptídeos Salivares/farmacologia , Proteínas de Artrópodes , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Ativação Enzimática , Humanos , Proteínas Recombinantes/farmacologia
19.
Rev Biol Trop ; 63(1): 285-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26299132

RESUMO

The physical dormancy of seeds has been poorly studied in species from tropical forests, such as the Atlantic Forest. This study aimed to examine the effect of moderate alternating temperatures on breaking the physical dormancy of seeds, the morphoanatomy and histochemistry of seed coats, and to locate the structure/region responsible for water entrance into the seed, after breaking the physical dormancy of seeds of two woody Fabaceae (subfamily Faboideae) species that occur in the Brazilian Atlantic Forest: Sophora tomentosa and Erythrina speciosa. To assess temperature effect, seeds were incubated in several temperature values that occur in the Atlantic Forest. For morphological and histochemical studies, sections of fixed seeds were subjected to different reagents, and were observed using light or epifluorescence microscopy, to analyze the anatomy and histochemistry of the seed coat. Treated and nonreated seeds were also analyzed using a scanning electron microscope (SEM) to observe the morphology of the seed coat. To localize the specific site of water entrance, the seeds were blocked with glue in different regions and also immersed in ink. In the present work a maximum temperature fluctuation of 15 degrees C was applied during a period of 20 days and these conditions did not increase the germination of S. tomentosa or E. speciosa. These results may indicate that these seeds require larger fluctuation of temperature than the applied or/and longer period of exposition to the temperature fluctuation. Blocking experiments water inlet combined with SEM analysis of the structures of seed coat for both species showed that besides the lens, the hilum and micropyle are involved in water absorption in seeds scarified with hot water. In seeds of E. speciosa the immersion of scarified seeds into an aniline aqueous solution showed that the solution first entered the seed through the hilum. Both species showed seed morphological and anatomical features for seed coats of the subfamily Faboideae. Lignin and callose were found around all palisade layers and the water impermeability and ecological role of these substances are discussed in the work.


Assuntos
Erythrina/crescimento & desenvolvimento , Germinação/fisiologia , Dormência de Plantas/fisiologia , Sementes/crescimento & desenvolvimento , Sophora/crescimento & desenvolvimento , Microscopia Eletrônica de Varredura
20.
Open Mind (Camb) ; 8: 462-482, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665546

RESUMO

There are important differences between central and peripheral vision. With respect to shape, contours retain phenomenal sharpness, although some contours disappear if they are near other contours. This leads to some uniform textures to appear non-uniform (Honeycomb illusion, Bertamini et al., 2016). Unlike other phenomena of shape perception in the periphery, this illusion is showing how continuity of the texture does not contribute to phenomenal continuity. We systematically varied the relationship between central and peripheral regions, and we collected subjective reports (how far can one see lines) as well as judgments of line orientation. We used extended textures created with a square grid and some additional lines that are invisible when they are located at the corners of the grid, or visible when they are separated from the grid (control condition). With respects to subjective reports, we compared the region of visibility for cases in which the texture was uniform (Exp 1a), or when in a central region the lines were different (Exp 1b). There were no differences, showing no role of objective uniformity on visibility. Next, in addition to the region of visibility we measured sensitivity using a forced-choice task (line tilted left or right) (Exp 2). The drop in sensitivity with eccentricity matched the size of the region in which lines were perceived in the illusion condition, but not in the control condition. When participants were offered a choice to report of the lines were present or absent (Exp 3) they confirmed that they did not see them in the illusion condition, but saw them in the control condition. We conclude that mechanisms that control perception of contours operate differently in the periphery, and override prior expectations, including that of uniformity. Conversely, when elements are detected in the periphery, we assign to them properties based on information from central vision, but these shapes cannot be identified correctly when the task requires such discrimination.

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