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1.
J Cell Mol Med ; 28(9): e18342, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693852

RESUMO

Urothelial carcinoma (UC) urgently requires new therapeutic options. Histone deacetylases (HDAC) are frequently dysregulated in UC and constitute interesting targets for the development of alternative therapy options. Thus, we investigated the effect of the second generation HDAC inhibitor (HDACi) quisinostat in five UC cell lines (UCC) and two normal control cell lines in comparison to romidepsin, a well characterized HDACi which was previously shown to induce cell death and cell cycle arrest. In UCC, quisinostat led to cell cycle alterations, cell death induction and DNA damage, but was well tolerated by normal cells. Combinations of quisinostat with cisplatin or the PARP inhibitor talazoparib led to decrease in cell viability and significant synergistic effect in five UCCs and platinum-resistant sublines allowing dose reduction. Further analyses in UM-UC-3 and J82 at low dose ratio revealed that the mechanisms included cell cycle disturbance, apoptosis induction and DNA damage. These combinations appeared to be well tolerated in normal cells. In conclusion, our results suggest new promising combination regimes for treatment of UC, also in the cisplatin-resistant setting.


Assuntos
Apoptose , Inibidores de Histona Desacetilases , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Bexiga Urinária , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Ftalazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia
2.
Cancer ; 126(2): 408-415, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580497

RESUMO

BACKGROUND: Given the major changes in internet use for health communication, the objective of the current study was to compare the internet use and wishes of cancer survivors between 2005 and 2017. METHODS: The authors drew a sample of 390 patients in 2005 and 539 patients in 2017 who were diagnosed with breast (128 patients in 2005 and 143 patients in 2017), prostate (96 patients in 2005 and 126 patients in 2017), or gynecologic (89 patients in 2005 and 188 patients in 2017) cancer or lymphoma (77 patients in 2005 and 82 patients in 2017) in 4 different hospitals for the periods 2002 through 2004 and 2014 through 2016. These patients were sent a paper-based questionnaire that contained 45 questions regarding demographics and 4 functions of internet use: content, communication, community, and e-health. RESULTS: The response in 2017 (53%) was lower than that in 2005 (75%). Survivors browsed the internet most frequently to search for information regarding cancer shortly after being diagnosed and while waiting for treatment. There was little change noted with regard to the relative importance attached to the various subjects. In 2017, significant increases were evident with regard to finances (+33%), health care insurance (+29%), and genetics and/or heritability (+27%). The wishes expressed in 2005 by patients were realized in part in 2017. CONCLUSIONS: A significant sample of cancer survivors in the Netherlands have indicated that the internet is an important source of information regarding their illness. However, little change was evident over the past 15 years with regard to patients' priorities regarding their wishes for internet use. The wishes of users in 2005 were found to accurately reflect the internet use of the majority of patients in 2017. The results of the current study support the belief that health care professionals should expand their online services and tailor them toward the needs and wishes of their patients.


Assuntos
Sobreviventes de Câncer/psicologia , Comunicação em Saúde/tendências , Comportamento de Busca de Informação , Internet/tendências , Neoplasias/terapia , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/psicologia , Países Baixos , Inquéritos e Questionários/estatística & dados numéricos
3.
Support Care Cancer ; 27(5): 1935-1944, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30215142

RESUMO

OBJECTIVES: According to the Common Sense Model of self-regulation, cancer survivors construct perceptions of their illness as a (mal)adaptive mechanism. These perceptions might impact on health care use. We aimed to explore the association between illness perceptions and health care use in stage I-II endometrial cancer (EC) survivors, and whether these associations differed by time since diagnosis. METHODS: A survey was conducted in 2008 by the population-based PROFILES registry among EC survivors diagnosed between 1999 and 2007. Survivors (n = 742, 77% response) completed the Brief Illness Perception Questionnaire (BIPQ) and questions on health care use in the past 12 months. Clinical data were accessed from the Netherlands Cancer Registry. Multiple logistic regression was used to evaluate the relationship between illness perceptions and health care use. RESULTS: Between 15 and 22% of the survivors had negative illness perceptions. Survivors with more negative perceptions on consequences, timeline, treatment control, identity, cognitive representation, concern, emotion, and emotional representation were more likely to make ≥ 1 visit to their family physician/general practitioner in relation to their cancer when compared with survivors with more positive illness perceptions. More negative perceptions on consequences, timeline, identity, and concern were associated with ≥ 2 general or cancer-related visits to the medical specialists. The association between negative illness perceptions and health care use was more prominent among long-term (>5 years post-diagnosis) EC survivors. CONCLUSIONS: Negative illness perceptions among EC survivors were associated with higher health care use. For individuals with maladaptive illness perceptions, visits to their health care provider may reduce worry about their illness. Future research might address the effects of intervening in maladaptive illness perceptions on use of health care in this category of survivors.


Assuntos
Sobreviventes de Câncer/psicologia , Atenção à Saúde/estatística & dados numéricos , Neoplasias do Endométrio/psicologia , Neoplasias do Endométrio/terapia , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Sobreviventes de Câncer/estatística & dados numéricos , Emoções , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Percepção , Sistema de Registros , Inquéritos e Questionários
4.
Cancers (Basel) ; 13(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34680250

RESUMO

High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women diagnosed with advanced stage disease. In this study, we investigate possible relations between survival and signal transduction pathway (STP) activity. We assessed the functional activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-ß) and canonical wingless-type MMTV integration site (Wnt) pathway in 85 primary tumor samples of patients with FIGO stage IIIC to IVB HGSC and disease-free survival (DFS) below 12 (n = 52) or over 24 months (n = 33). There were no significant differences in median pathway activity between patients with a short and long DFS. In univariate Cox proportional hazards analysis, ER pathway activity was related to a favorable DFS and overall survival (OS) in postmenopausal women (p = 0.033 and p = 0.041, respectively), but not in premenopausal women. We divided the postmenopausal group into subgroups based on ER pathway activity quartiles. Survival analysis revealed that postmenopausal women in the lowest ER quartile had a shorter DFS and OS (log-rank p = 0.006 and p < 0.001, respectively). Furthermore, we were able to form subgroups of patients based on an inverse relation between ER and PI3K pathway activity. In conclusion, in postmenopausal patients with advanced stage HGSC, a poorer survival outcome was associated with low functional ER pathway activity.

5.
Langmuir ; 26(21): 16503-9, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20973585

RESUMO

The transformation of a poly(tetrafluoroethylene) (PTFE) hydrophobic surface into a superhydrophobic one using a low pressure RF plasma is explored using optical emission spectrometry (OES), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) measurements, mass measurements, and atomic force microscopy (AFM). It is shown that the increase in contact angle is due to an increase of roughness provoked by a chemical etching of the surface. We propose a molecular mechanism for etching that requires the simultaneous presence of atomic oxygen and negatively charged species (electrons) at the PTFE surface.


Assuntos
Oxigênio/química , Politetrafluoretileno/química , Politetrafluoretileno/síntese química , Adsorção , Elétrons , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Propriedades de Superfície
6.
Otol Neurotol ; 28(1): 61-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17195748

RESUMO

OBJECTIVE: To analyze predictive factors of outcome after ossiculoplasty using a standard ossicular prosthesis system. STUDY DESIGN: Retrospective review of 140 ossiculoplasties, performed by the same senior surgeon, with titanium prostheses. SETTINGS: Academic hospital and tertiary referral center. PATIENTS: All patients undergoing ossiculoplasty with Spiggle and Theis or Kurz titanium total and partial prostheses. Documented, postoperative follow-up had to be provided. A total of 129 patients (140 ears; 53 men and 76 women) were evaluated. INTERVENTIONS: These included ossiculoplasties using 75 Spiggle and Theis prostheses (30 partial and 45 total) and 65 Kurz prostheses (35 partial and 30 total). MAIN OUTCOME MEASURES: Mean preoperative and postoperative air-bone gaps and the changes in mean hearing loss were analyzed using a four-frequency (500, 1,000, 2,000, and 3,000 Hz) pure tone average. Success rate was defined as postoperative air-bone gap within 20 dB. A one-way analysis of variance was used to analyze group differences. A multivariate statistical analysis was then undertaken to define the significant factors. RESULTS: There were no statistical difference between the Spiggle and Theis and the Kurz prostheses. Multivariate statistical analysis has identified the predictive value of the presence or absence of the malleus handle and the mucosal status of the middle ear in the prognosis of ossiculoplasties. CONCLUSION: Anatomical and technical factors diversely affect the functional outcome of tympano-ossiculoplasties. A better knowledge of their predictive value will enable accurate, preoperative, individual assessment when counseling patients with regard to the success of any proposed intervention. The use of these factors will also permit precise matching of future series to allow accurate comparisons.


Assuntos
Colesteatoma da Orelha Média/cirurgia , Ossículos da Orelha/cirurgia , Substituição Ossicular/métodos , Adolescente , Adulto , Idoso , Audiometria de Tons Puros , Criança , Pré-Escolar , Colesteatoma da Orelha Média/complicações , Colesteatoma da Orelha Média/patologia , Ossículos da Orelha/fisiopatologia , Orelha Média/patologia , Orelha Média/cirurgia , Feminino , Seguimentos , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Masculino , Martelo/cirurgia , Processo Mastoide/cirurgia , Pessoa de Meia-Idade , Mucosa/patologia , Mucosa/cirurgia , Prótese Ossicular , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Percepção da Fala/fisiologia , Cirurgia do Estribo , Titânio/uso terapêutico , Timpanoplastia
7.
Eur J Emerg Med ; 16(3): 124-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19262396

RESUMO

Torsion of the ovary or fallopian tube is a rare acute gynaecological disorder, seen by different medical specialists. The diverse clinical presentation is one of the main reasons this diagnosis is frequently missed at first presentation. For the preservation of ovarian function it is of utmost importance to diagnose an ovarian torsion at an early stage. We will describe the medical history of three patients with a torsion of one of the ovaries to illustrate the variety of clinical presentation. A medical history of pelvic operations or enlarged ovaries often predisposes to torsion of the ovary or fallopian tube. Treatment policy will differ depending on the stage of life. Ovariopexy can be considered to prevent the ovary from torsion and to maintain its function. Torsion of the ovary is an acute gynaecological disorder with an incidence of 3% in a series of acute gynaecological complaints. It is a disorder in which the ovary and the fallopian tube can be affected, combined as well as separated. Although every specialist is familiar with the disorder, the diagnosis in acute presentation is frequently missed. To bring this entity and its great variability in clinical presentation into focus once again, we will highlight three patients out of a series of 13. Furthermore, we will discuss the possible causes of the disorder and present a proposition for treatment.


Assuntos
Dor Abdominal/etiologia , Doenças Ovarianas/diagnóstico , Anormalidade Torcional/diagnóstico , Adulto , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Emergências , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Doenças Ovarianas/diagnóstico por imagem , Doenças Ovarianas/etiologia , Doenças Ovarianas/cirurgia , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/etiologia , Anormalidade Torcional/cirurgia , Ultrassonografia
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