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1.
Breast Care (Basel) ; 19(4): 197-206, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39185130

RESUMO

Introduction: Breast cancer (BC) is the most common cancer among women globally. Vitamin D has been considered a protective factor; however, its relationship with any aspect of the disease remains controversial. Methods: A cross-sectional, single-center clinical study was conducted between 2015 and 2018, including 141 women diagnosed with BC and 239 women in the control group, with mean ages of 43.1 and 41.7 years, respectively (p = 0.103). Serum levels of vitamin D and lipid profile were measured. Clinical and nutritional data were obtained through interviews and medical records. Results: The vitamin D dosage presented an average value of 25.5 ng/mL and 31.0 ng/mL in the case and control groups, respectively (p < 0.001). The vitamin D cut-off point for discriminating the presence of BC was 27.45 ng/mL. Additionally, low-density lipoprotein cholesterol levels were higher in the case group (121.4 mg/dL) compared to the control group (110.7 mg/dL) (p = 0.002), whereas high-density lipoprotein cholesterol levels were lower in the case group (47.6 mg/dL) compared to the control group (53.3 mg/dL) (p = 0.001). Alcohol consumption was significantly higher in the case group than in the control group (2.7 vs. 5.3 doses/day; p < 0.001). Conclusion: The results indicate a significant association between lower vitamin D levels and BC, persisting after multivariate analysis (p < 0.001). These findings could inform prevention strategies, highlighting the importance of maintaining adequate vitamin D levels and potentially identifying a risk group.

2.
Cancer Med ; 12(15): 16129-16141, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37485802

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. METHODS: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. RESULTS: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574). CONCLUSIONS: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.


Assuntos
Neoplasias do Sistema Nervoso Central , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias do Sistema Nervoso Central/secundário , Genes BRCA2 , Predisposição Genética para Doença , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
3.
Sports Med Health Sci ; 5(2): 128-136, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37424527

RESUMO

This study aimed to evaluate the efficacy of an individualized remote exercise program on the improvement of body composition and physical fitness of a heterogeneous group of patients who completed breast cancer treatment. This prospective study included 107 women aged 18 to 60, shortly after curative treatment for localized breast cancer, at the Erasto Gaertner Cancer Hospital (HEG) in Curitiba, PR, Brazil. Body composition, maximal oxygen consumption, and muscle resistance were evaluated after nine months of intervention while considering adherence to the program, level of physical activity, presence of binge eating disorder, tumor classification, and treatment type. Seventy-eight women (72.8%) adhered to the training program. Adherent participants showed significant changes in body mass ([-4.3 â€‹± â€‹3.6] kg; p â€‹< â€‹0.000 1), body mass index ([-1.6 â€‹± â€‹1.5] kg·m-2; p â€‹< â€‹0.000 1), body fat (-3.4% â€‹± â€‹3.1%; p â€‹< â€‹0.000 1), maximal oxygen consumption ([7.5 â€‹± â€‹2.0] ml·kg-1·min-1); p â€‹< â€‹0.000 1), and abdominal resistance ([11.2 â€‹± â€‹2.8] reps; p â€‹< â€‹0.000 1). In contrast, these variables did not change significantly in the non-adherent group. Among the adherent participants, those subclassified in the severe binge group showed a more noticeable reduction in body mass, body mass index, and body fat (p â€‹< â€‹0.05) than those in the non-binge group. Individualized remotely-guided physical exercise programs can improve the body composition and physical fitness of women undergoing post-breast cancer surveillance, regardless of pathological history or treatment.

4.
Mol Genet Genomic Med ; 11(4): e2136, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36625343

RESUMO

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by pathogenic variants in VHL gene. The common manifestations include hemangioblastomas (HB) of the central nervous system (CNS) and retina (RH); pheochromocytoma (PHEO); clear cell renal cell carcinoma (ccRCC); pancreatic and renal cysts (PRC) and pancreatic neuroendocrine neoplasm (PNEN). METHODS: The first characterization of VHL in Brazil was published in 2003 and included 20 families with a history of VHL. The aim of this study was to expand the previous Brazilian cohort to include more families, as well as to collect prospectively both clinical and molecular characteristics of patients with VHL to build the VHL Brazilian Registry (VHLBR). Patients with VHL were selected through review of data from medical records of experts and from social networks of support for families with VHL in Brazil. RESULTS: A total of 142 subjects representing 62 unrelated Brazilian families with VHL were registered. The mean age of VHL onset was 28.78 years old and 128 individuals (90.1%) had at least one VHL-related lesion. CNS HB was the most common manifestation occurring in 91 (71%) patients, followed by multiple PRC (48.4%), RH (39.8%), ccRCC (28.9%), PHEO (12.5%) and PNEN (7.8%). Of the 97 subjects whose presence of VHL variants was confirmed, 51 (52.6%) had missense variants, 22 (22.7%) large deletions, 10 (10.3%) frameshift, 7 (7.2%) splice site, 4 (4.1%) nonsense and 3 (3.1%) in-frame deletions. Regarding surveillance, 115 (81%) participants had at least one physician responsible for their outpatient follow-up; however, 69 (60%) of them did not report a regular frequency of tests. CONCLUSION: We built the largest prospective VHLBR with organized collections of clinical and genetic data from families with VHL, which will be helpful to guide policies for VHL care and oncogenetics in Brazil. Although there have been improvements in diagnosis and clinical screening methods, VHL care in Brazil is still deficient, especially regarding surveillance and regular medical appointments with experts.


Assuntos
Carcinoma de Células Renais , Hemangioblastoma , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Adulto , Doença de von Hippel-Lindau/epidemiologia , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/diagnóstico , Brasil/epidemiologia , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Estudos Prospectivos , Neoplasias Renais/genética
5.
J Surg Oncol ; 126(1): 10-19, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35689574

RESUMO

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.


Assuntos
Neoplasias da Mama , Ginecologia , Neoplasias Ovarianas , Oncologia Cirúrgica , Brasil/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Neoplasias Ovarianas/cirurgia
6.
J Pers Med ; 12(4)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35455627

RESUMO

Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinico-pathological factors. Twenty-five patients (16.8%) had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in univariate analysis (p = 0.045) and after adjustment for stage (HR 2.52; 95% CI 1.13-5.65; p = 0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p = 0.158; adjusted for stage: p = 0.117). Hence, in our small exploratory study, the link between impaired tamoxifen metabolism and early breast cancer recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold.

7.
J Community Genet ; 13(1): 19-29, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34623598

RESUMO

Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC); however, it is still underrecognized and underdiagnosed. While international guidelines gravitate towards universal screening, the underuse of screening methods has been reported in real-world scenarios. This study aims to evaluate screening for LS among patients diagnosed with CRC in a public cancer center in Brazil and evaluate access to genetic counseling and testing for abnormal screens. For that purpose, all patients with CRC registered in our institution from July 2012 to December 2018 had their charts reviewed. Demographic and clinical characteristics were noted, as well as immunohistochemistry and microsatellite instability analysis results, when available. After applying exclusion criteria, a total of 1234 charts were reviewed. Among these, 257 patients were screened for LS, making up a 20.8% screening rate; when considering Jerusalem criteria, screening rate was 24.5%; for Bethesda criteria, it was 35.1%. Almost 80% of patients fulfilling Amsterdam criteria I/II were screened. There were 64 abnormal screens, from which 40 (62.5%) underwent genetic counseling and 12 (18.7%) underwent genetic testing. We concluded that overall screening rates for LS among CRC patients in a public cancer center in Brazil are low, and still very guided by stringent clinical criteria. Referral to genetic counseling and access to testing is limited, calling the whole process into question. Public policies aiming to raise awareness on hereditary cancer and include genetic testing in the public health system could help improve this scenario.

8.
Cancers (Basel) ; 13(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298749

RESUMO

Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.

9.
Clin Pract ; 11(2): 205-215, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917271

RESUMO

INTRODUCTION: Phyllodes tumor (PT) of the breast, particularly malignant phyllodes tumor (mPT), is a rare fibroepithelial neoplasm. A complex diagnosis is based on pathologic, radiologic, and clinical findings, with controversies about what is the best therapeutic strategy. OBJECTIVE: Our objective was to provide an overview of the clinical, pathologic, and therapeutic aspects of this rare tumor. CONCLUSIONS: mPT is a rare presentation of breast cancer and a challenge in clinical practice. A multidisciplinary approach should take into account some aspects like pathogenic mutations and hereditary syndromes. Oncologic surgery is the fundamental approach, and the use of adjuvant therapies is still controversial due to the lack of clinical trials. Treatment recommendations should be individualized according to patient risk and preferences. Prospective studies are fundamental to clarifying the best treatment for these tumors.

10.
Sci Rep ; 11(1): 6768, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762648

RESUMO

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Cortisona/sangue , Metilação de DNA , Depressão/genética , Sobrepeso/genética , Receptores de Glucocorticoides/genética , Adulto , Biomarcadores , Ilhas de CpG , Estudos Transversais , Depressão/metabolismo , Suscetibilidade a Doenças , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/metabolismo , Receptores de Glucocorticoides/metabolismo , Fatores Socioeconômicos , Adulto Jovem
11.
Cancers (Basel) ; 12(7)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659967

RESUMO

Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir-Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.

12.
Clin Transl Sci ; 13(2): 284-292, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31573754

RESUMO

Tamoxifen efficacy in breast cancer is suspected to depend on adherence and intact drug metabolism. We evaluated the role of adherence behavior and pharmacogenetics on the formation rate of (Z)-endoxifen. In 192 Brazilian patients, we assessed plasma levels of tamoxifen and its metabolites at 3, 6, and 12 months of treatment (liquid-chromatography tandem mass spectrometry), adherence behavior (Morisky, Green, and Levine medication adherence scale), and cytochrome P450 2D6 (CYP2D6) and other pharmacogene polymorphisms (matrix-assisted laser-desorption-ionization time of flight) mass spectrometry, real-time polymerase chain reaction). Adherence explained 47% of the variability of tamoxifen plasma concentrations (P < 0.001). Although CYP2D6 alone explained 26.4%, the combination with adherence explained 40% of (Z)-endoxifen variability at 12 months (P < 0.001). The influence of low adherence to not achieving relevant (Z)-endoxifen levels was highest in patients with noncompromised CYP2D6 function (relative risk 3.65; 95% confidence interval 1.48-8.99). As a proof-of-concept, we demonstrated that (Z)-endoxifen levels are influenced both by patient adherence to tamoxifen and CYP2D6, which is particularly relevant for patients with full CYP2D6 function.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2D6/genética , Adesão à Medicação/estatística & dados numéricos , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/farmacocinética , Brasil , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Citocromo P-450 CYP2D6/metabolismo , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Testes Farmacogenômicos/estatística & dados numéricos , Variantes Farmacogenômicos , Autorrelato/estatística & dados numéricos , Tamoxifeno/análogos & derivados , Tamoxifeno/sangue , Tamoxifeno/metabolismo , Tamoxifeno/farmacocinética , Adulto Jovem
13.
Mastology (Impr.) ; 28(3): 134-155, jul.-set.2018.
Artigo em Inglês | LILACS | ID: biblio-967745

RESUMO

Objective: Genetic-related breast cancer has a tendency to manifest earlier and to be more aggressive than sporadic cancer. There are few studies evaluating the prevalence and incidence of hereditary breast and ovarian cancer (HBOC) among Brazilians. In order to improve assistance, efforts to characterize the population at risk of HBOC could help to formulate locally designed guidelines. Methodology: Descriptive retrospective study in Hospital Erasto Gaertner's service of Oncogenetics, in Curitiba, state of Paraná, Brazil. We included individuals at-risk for HBOC, according to the National Comprehensive Cancer Network (NCCN) criteria, who had performed genetic tests for HBOC. We collected complete family history, presented as heredograms. We excluded families with inappropriate family history. Results: Of the 27 patients analyzed (total of 25 families), 7% were asymptomatic, 8% had ovarian cancer and 85% had breast cancer. Mutations were found in 29.6%, 6 cases of BRCA1, 1 of BRCA2 and 1 of TP53. Triple negative was the most common reported subtype, representing 60% of breast cancers; among patients with identified pathogenic variants, 2 were BRCA2 mutated and 1 TP53 mutated. The mean age of diagnosis was 40 years for those identified as probands on heredograms; in the generation above, it was 52,5, and in the below, 33, suggesting the antecipation phenomena Two new mutations were identified in Brazilian population, both in BRCA1: c.4258 G>A and c.5345 G>A. The most frequent NCCN criteria were number 2, 9, 8 and 4. Estimated penetrance was 22%. Conclusion: This is the first descriptive study in the population at-risk for HBOC in the state of Paraná. We could identify two new pathogenic variants of BRCA1 in Brazilian population. A comprehensive family history was included in the study, depicted as heredograms of each family. Despite the low number of patients, the main results are in agreement with previous studies


Objetivo: Os carcinomas de mama hereditários têm a tendência de se manifestar precocemente e serem mais agressivos do que os esporádicos. São poucos os estudos que avaliam a prevalência e a incidência da síndrome de câncer de mama e ovário hereditário (SCMOH) na população brasileira. No intuito de melhorar a assistência prestada, a análise das características encontradas na população em risco para SCMOH ajudaria a formulação de protocolos regionais para a abordagem desses pacientes. Metodologia: Estudo descritivo retrospectivo realizado no serviço de Oncogenética do Hospital Erasto Gaertner em Curitiba, Paraná. Incluímos indivíduos em risco para SCMOH pelos critérios estabelecidos pela National Comprehensive Cancer Network (NCCN) e que realizaram testes genéticos para SCMOH. Coletamos o histórico familiar completo, apresentado na forma de heredograma. Foram excluídas famílias com histórico familiar inapropriado. Resultados: Das 27 pacientes analisadas (total de 25 famílias), 7% eram assintomáticas, 8% tiveram câncer de ovário e 85%, câncer de mama. Mutações foram encontradas em 29,6%, sendo 6 casos de BRCA1, 1 de BRCA2 e 1 de TP53. Tumores triplo negativos foram os mais encontrados entre os subtipos, representando 60% dos carcinomas de mama; dentre os pacientes com variantes patogênicas, 2 eram de mutações em BRCA2 e 1 em TP53. A média de idade entre as pacientes foi de 40 anos entre probandas dos heredogramas; na geração superior, foi de 52,5 anos e na inferior, de 33, sugerindo o fenômeno de antecipação. Duas novas mutações foram descritas na população brasileira, as duas sendo em BRCA1: c.4258 G>A e c.5345 G>A. Os critérios NCCN mais encontrados foram os de número 2, 9, 8 e 4. A penetrância estimada foi de 22%. Conclusão: Este foi o primeiro estudo descritivo de uma população em risco para SCMOH no estado do Paraná. Encontramos duas novas mutações que não haviam sido descritas na população brasileira até então. Foi realizada a análise detalhada do histórico familiar das pacientes, sendo descrita e detalhada em heredogramas para cada família. Apesar do baixo número de indivíduos analisados, os resultados principais foram de acordo com o encontrado em estudos prévios

14.
Ecancermedicalscience ; 11: 716, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28194228

RESUMO

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.

15.
Rev. bras. mastologia ; 24(3): 82-87, jul-set 2014. tab
Artigo em Português | LILACS-Express | LILACS | ID: lil-782261

RESUMO

A Sindrome de Câncer de Mama e Ovário Hereditários é a principal causa hereditária de câncer de mama. Nesse artigo, abordamos os principais fatos relevantes à epidemiologia, rastreamento, medidas de redução de risco e características patologicas que podem nos ajudar a estabelecer nossa atuação em relação a essa patologia em 2015.


Hereditary breast?ovarian cancer syndrome is the main cause of hereditary breast cancer. In this paper we discuss the main facts relevant to the epidemiology, screening, risk reduction measures and pathological caractheristics that can help us in our practice in 2015.

16.
Proteins ; 81(2): 349-63, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23011899

RESUMO

The von Hippel-Lindau tumor suppressor protein (pVHL) plays a central role in the oxygen-sensing pathway by regulating the degradation of the hypoxia-inducible factor (HIF-1α). The capture of HIF-1α by pVHL is regulated by an oxygen-dependent hydroxylation of a specific conserved prolyl residue. The VHL gene is mutated in the von Hippel-Lindau cancer predisposition syndrome, which is characterized by the development of highly vascularized tumors and is associated with constitutively high levels of HIF-1α. The disturbance of the dynamic coupling between HIF-1α and pVHL bearing the commonly found mutation F76del was experimentally confirmed but the mechanism of such complex disruption is still not clear. Performing unbiased molecular dynamics simulations, we show that the F76del mutation may enlarge the HIF binding pocket in pVHL and induce the formation of an internal cavity in the hydrophobic core of the ß-domain, which can lead to a partial destabilization of the ß-sheets S1, S4, and S7 and a consequent loss of hydrogen bonds with a conserved recognition motif in HIF. The newly formed cavity has a significant druggability score and may be a suitable target for stabilizing ligands. Studies of this nature may help to fill the information gap between genotype-phenotype correlations with details obtained at atomic level and provide basis for future development of drug candidates, such as pharmacological chaperones, with the specific aim of reverting the dysfunction of such pathological protein complexes found in patients with VHL.


Assuntos
Biologia Computacional/métodos , Descoberta de Drogas/métodos , Simulação de Dinâmica Molecular , Proteína Supressora de Tumor Von Hippel-Lindau/química , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mutação/genética , Ligação Proteica , Conformação Proteica , Estabilidade Proteica , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
17.
Arch Gynecol Obstet ; 283(4): 855-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20458489

RESUMO

PURPOSE: This study aims to analyze serum albumin levels (SAL) in relation to concentrations of vascular endothelial growth factor (VEGF) from peripheral plasma, infundibular plasma, peritoneal fluids and the peritoneal burden of VEGF of patients with epithelial ovarian cancer. METHODS: Exploratory analyses of SAL in 39 patients and its relation to mean concentrations of VEGF from the origins are described above. Statistical analyses comprised Student's t test, Mann-Whitney test and Pearson's and Spearman's correlation coefficient. RESULTS: Both infundibular concentrations of VEGF and the peritoneal burden of VEGF showed significant differences between SAL dichotomized at 3 g/dl. Concentrations of VEGF in peritoneal fluids were not significant in relation to SAL. Peripheral plasma VEGF levels did not show any linear correlation with SAL. Indeed, SAL showed a significant negative linear correlation (p < 0.001) to infundibular plasma as well as the peritoneal burden of VEGF (p = 0.004). CONCLUSIONS: Infundibular mean concentrations of VEGF may contribute to reduce SAL in advanced staging rather than the peripheral plasma concentrations of this glycoprotein. The peritoneal burden of VEGF may also aid in decreasing levels of serum albumin.


Assuntos
Adenocarcinoma/sangue , Albuminas/metabolismo , Líquido Ascítico/metabolismo , Neoplasias Ovarianas/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
18.
Rev Assoc Med Bras (1992) ; 56(5): 563-7, 2010.
Artigo em Inglês, Português | MEDLINE | ID: mdl-21152829

RESUMO

OBJECTIVE: To report practical experience in obtaining consent for a retrospective study conducted at the Brazilian National Cancer Institute (INCA). The study involved review of medical records and analysis of paraffin blocks of patients surgically treated for colon cancer between 2000 and 2004. Attempts to obtain informed consent were made in compliance with the resolution 196/96 of the Brazilian National Health Council and determination of INCA Research Ethics Committee. METHODS: At scheduled appointments, we could approach only four patients for consent during three months. After attempting contact by phone, an information sheet summarizing the content of informed consent, two copies of the consent form and a prepaid return envelope were then mailed to the patients. RESULTS: Of the 155 consent forms mailed, 115 were returned (74%). Of these, 111 patients gave consent to participate in the study, one refused consent, and we were informed that three patients had died. The time course of return of these forms ranged from 2 to 89 days (median: 10 days). Attempts to contact patients by phone were successful in 60 out of 160 cases (37.5%). The Research Ethics Committee waived the requirement of consent for those who had died or not responded. Overall mailing cost was R$ 1,004.40. CONCLUSION: Obtaining consent from patients by phone and mail for a retrospective clinical study is feasible. Most patients responded to contact and gave consent to participate. However, the process entails costs and risks that cannot be overlooked.


Assuntos
Bancos de Espécimes Biológicos , Consentimento Livre e Esclarecido/estatística & dados numéricos , Consentimento Livre e Esclarecido/normas , Entrevistas como Assunto , Serviços Postais , Humanos , Entrevistas como Assunto/estatística & dados numéricos , Serviços Postais/economia , Serviços Postais/estatística & dados numéricos , Fatores de Tempo
19.
Fam Cancer ; 9(4): 635-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20567917

RESUMO

von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome that predisposes to the development of a variety of benign and malignant tumours, especially cerebellar haemangioblastomas, retinal angiomas and clear-cell renal cell carcinomas (RCC). The etiology and manifestations are due to germline and somatic mutations in the VHL tumour suppressor gene. VHL disease is classified into type 1 and type 2, showing a clear genotype-phenotype correlation, as type 2 is associated with phaeochromocytoma and essentially caused by missense mutations. The aim of this study is to characterize the phenotype and genotype of families with VHL disease. Eighteen of twenty patients from ten unrelated families underwent genetic testing, nine of them fulfilled VHL disease criteria and one had an apparently sporadic cerebellar haemangioblastoma. Four different germline mutations in the VHL gene were identified: c.226_228delTTC (p.Phe76del); c.217C > T (p.Gln73X); IVS1-1 G > A and IVS2-1 G > C. The first three mutations were associated with type 1 disease and the last one with type 2B, which had never been identified in the germline. The transcriptional processing of a novel splice-site mutation was characterised. Three type 1 VHL families showed large deletions of the VHL gene, two of them encompassed the FANCD2/C3orf10 genes and were not associated with renal lesions. We also suggest that such families should be subclassified according to the risk of RCC and the extent of the VHL gene deletions. This study highlights the need for a through clinical and molecular characterisation of families with VHL disease to better delineate its genotype-phenotype correlation.


Assuntos
Carcinoma de Células Renais/genética , Deleção de Genes , Neoplasias Renais/genética , Mutação/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adolescente , Adulto , Brasil , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Criança , Análise Mutacional de DNA , DNA de Neoplasias/genética , Família , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Íntrons , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Adulto Jovem , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/patologia
20.
Int J Gynaecol Obstet ; 109(2): 113-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20167321

RESUMO

OBJECTIVE: To determine whether peripheral plasma concentration, peritoneal fluid concentration, and/or peritoneal vascular endothelial growth factor (VEGF) burden can predict the possibility of optimal cytoreduction in women with epithelial ovarian carcinoma (EOC); and if so, to determine cutoff values below which optimal cytoreduction is likely to occur. METHODS: We measured plasma VEGF concentration, peritoneal VEGF concentration, and VEGF burden in 46 women undergoing cytoreductive surgery. Univariate analysis, bivariate analysis, correlation tests, and stepwise regression were performed with cytoreduction as the outcome. RESULTS: The VEGF burden best predicted the outcome. The area under the curve was 0.84 and the log-transformed cutoff value was 15.52 log pg. Overall, the chance of optimal cytoreduction was 11 times greater when the VEGF burden was less than 15.52 log pg. For women with advanced disease, the chance was 6 times greater below this value. CONCLUSION: The VEGF burden may quantify tumor activity, and it could be used when selecting patients likely to benefit from induction chemotherapy before undergoing cytoreductive surgery.


Assuntos
Adenocarcinoma/cirurgia , Biomarcadores Tumorais/análise , Neoplasias Ovarianas/cirurgia , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Ascítico/química , Biomarcadores Tumorais/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , Prognóstico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
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