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1.
Ann Surg Oncol ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748122

RESUMO

INTRODUCTION: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is increasingly used for both breast cancer (TNSM) and risk reduction (RRNSM). The aim of the study is to report the results of the INSPIRE registry assessing health-related quality of life (HRQoL) comparing baseline and 1-year follow-up, regarding surgical indications and chemotherapy (CT) received. METHODS: INSPIRE is a prospective database including women undergoing NSM and IBR from 18 countries. HRQoL was measured using EORTC QLQC30 and QLQ-BR23 before surgery and after 1 year. RESULTS: A total of 677 women were included, of whom 537 (79.3%) underwent TNSM and 140 (21.6%) RRNSM: in total, 806 NSM (556 TNSM and 250 RRNSM). Nipple involvement was present in 7.73% of TNSM and incidental carcinoma in 1.2% of the RRNSM group. Out of the overall 537 patients with systemic treatment, 177 (32.96%) received neoadjuvant chemotherapy (NCT) and 118 (21.92%) adjuvant chemotherapy (CT). A total of 227 patients (28.16%) developed at least one complication postoperatively, 164 (29.5%) in the TNSM group and 63 (25.2%) in the RRNSM group. The TNSM group improved in global health status and emotional functioning after 1 year. No differences were found when comparing HRQoL at 1 year between patients who received NCT and those who received adjuvant CT. The RRNSM group showed improvement in HRQoL, with better emotional functioning and fatigue after 1 year. CONCLUSIONS: This registry reports HRQoL findings after NSM. The impact of CT on worse HRQoL is independent from its timing. Patients with RRNSM showed an improved HRQoL at 1-year follow-up. Discussion of HRQoL outcomes with patients will facilitate the informed decision-making when considering NSM.

3.
Breast ; 60: 131-137, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34624755

RESUMO

BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.

4.
Breast ; 60: 155-162, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34627117

RESUMO

INTRODUCTION: Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). MATERIAL AND METHODS: Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. RESULTS: Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. CONCLUSION: Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve.

5.
Ann Surg Oncol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647202

RESUMO

INTRODUCTION: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). METHODS: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. RESULTS: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. CONCLUSIONS: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

7.
JMIR Form Res ; 5(5): e28668, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970120

RESUMO

BACKGROUND: Several mobile apps have been designed for patients with a diagnosis of cancer. Unfortunately, despite the promising potential and impressive spread, their effectiveness often remains unclear. Most mobile apps are developed without any medical professional involvement and quality evidence-based assessment. Furthermore, they are often implemented in clinical care before any research is performed to confirm usability, appreciation, and clinical benefits for patients. OBJECTIVE: We aimed to develop a new smartphone app (Centro di Senologia della Svizzera Italiana [CSSI]) specifically designed by breast care specialists and patients together to help breast cancer patients better understand and organize their journey through the diagnosis and treatment of cancer. We describe the development of the app and present assessments to evaluate its feasibility, usefulness, and capability to improve patient empowerment. METHODS: A mixed method study with brief longitudinal quantitative data collection and subsequent qualitative semistructured interviews was designed. Twenty breast cancer patients participated in the study (mean age 51 years, SD 10 years). The usability of the app, the user experience, and empowerment were measured after 1 month. The semistructured interviews measured the utility of the app and the necessary improvements. RESULTS: The app received good responses from the patients in terms of positive perception of the purpose of the app (7/20, 35%), organizing the cure path and being aware of the steps in cancer management (5/20, 25%), facilitating doctor-patient communication (4/20, 20%), and having detailed information about the resources offered by the hospital (2/20, 10%). Correlation and regression analyses showed that user experience increased the level of empowerment of patients (B=0.31, 95% CI 0.22-0.69; P=.009). The interviews suggested the need to constantly keep the app updated and to synchronize it with the hospital's electronic agenda, and carefully selecting the best time to offer the tool to final users was considered crucial. CONCLUSIONS: Despite the very small number of participants in this study, the findings demonstrate the potential of the app and support a fully powered trial to evaluate the empowering effect of the mobile health app. More data will be gathered with an improved version of the app in the second phase involving a larger study sample.

8.
Clin Chem Lab Med ; 59(9): 1501-1506, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-33915610

RESUMO

BACKGROUND: Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. CONTENT: A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia" was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013-2015 and 2017-2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. SUMMARY: For the final analysis, we included 361 articles (2013-2015, n=169; 2017-2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. OUTLOOK: Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013-2015 and the 2017-2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique.

9.
Cancers (Basel) ; 13(9)2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923153

RESUMO

BACKGROUND: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. METHODS: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. RESULTS: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin's disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). CONCLUSION: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.

10.
Eur J Surg Oncol ; 47(4): 796-803, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33097334

RESUMO

INTRODUCTION: Risk of breast cancer increases with age and very few data are available in patients older than 89. METHODS: A retrospective analysis on patients aged 89 and older treated between 2008 and 2019 at our certified breast center. The aim was to analyze clinical characteristics, decision-making, treatment, outcomes and open questions regarding this subpopulation for which there is a lack of guidelines. RESULTS: 58 patients included. Tumor characteristics were analyzed, 85% patients underwent surgery of which 44% had a mastectomy. The median follow-up and overall survival were 20 and 76 months, respectively.The median survival of metastatic and non-metastatic patients were 14 and 50 months, respectively. Most patients did not receive any adjuvant treatment and among these 14% had a relapse. CONCLUSIONS: Elderly patients should not be under or over-treated because of their age; they represent a large heterogeneous group deserving a sub-stratification for a better tailored treatment.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma in Situ/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Recidiva Local de Neoplasia/patologia , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundário , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Mastectomia , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
11.
Eur J Surg Oncol ; 46(4 Pt B): 717-736, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32075718

RESUMO

The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained breast surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has been developed by a panel of experts from across Europe and has been validated by professional breast surgery societies in Europe. The curriculum maps closely to the syllabus of the Union of European Medical Specialists (UEMS) Breast Surgery Exam, the UK FRCS (breast specialist interest) curriculum and other professional standards across Europe and globally (USA Society of Surgical Oncology, SSO). It is envisioned that this will serve as the basis for breast surgery training, examination and accreditation across Europe to harmonise and raise standards as breast surgery develops as a separate discipline from its parent specialties (general surgery, gynaecology, surgical oncology and plastic surgery). The curriculum is not static but will be revised and updated by the curriculum development group of the European Breast Surgical Oncology Certification group (BRESO) every 2 years.


Assuntos
Doenças Mamárias/diagnóstico , Doenças Mamárias/terapia , Currículo/normas , Oncologia Cirúrgica/educação , Oncologia Cirúrgica/normas , Mama/anatomia & histologia , Mama/fisiologia , Mama/cirurgia , Doenças Mamárias/fisiopatologia , Certificação/métodos , Certificação/normas , Competência Clínica/normas , Educação Médica/normas , Europa (Continente) , Bolsas de Estudo/normas , Humanos , Internato e Residência/normas
12.
Crit Rev Oncol Hematol ; 144: 102828, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710955

RESUMO

Granular cell tumors are rare soft tissue tumors; they are almost never malignant, but can mimic a carcinoma clinically, radiologically and microscopically. The finding of a suspicious lump often entails subsequent diagnostic procedures that can pose significant anxiety on patients before reaching a challenging differential diagnosis. The physical and psychological burden is even more significant when such findings occur during the follow up of a previous oncologic condition. Sometimes the fear for a potential local or distant recurrence can be responsible for a misdiagnosis and lead to patient overtreatment.


Assuntos
Neoplasias da Mama , Tumor de Células Granulares , Mama , Carcinoma , Diagnóstico Diferencial , Feminino , Humanos , Pesquisa Interdisciplinar , Recidiva Local de Neoplasia
13.
Breast Cancer Res Treat ; 172(3): 523-537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30182349

RESUMO

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Subcutânea/métodos , Consenso , Feminino , Humanos , Mastectomia Subcutânea/efeitos adversos , Necrose , Mamilos/patologia , Retalhos Cirúrgicos/patologia
14.
Breast ; 33: 83-90, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28288387

RESUMO

INTRODUCTION: Delay between clinical presentation and treatment of breast cancer (BC) can significantly impact mortality. We aimed at drawing a picture of women with locally advanced breast cancer (LABC) treated at our Breast Unit and at investigating factors associated with treatment delay. MATERIAL AND METHODS: A retrospective descriptive analysis, using a specific 28-item semi-structured questionnaire, was conducted in 67 patients diagnosed with T4 BC. RESULTS: Nearly a third of our patients had at least one known predisposing factor for LABC. 42% of patients did not perform routine medical breast checks, 49% reported indifference as the first feeling and 47% waited at least 3 months before seeking medical attention. The reasons for diagnostic delay were different in the various age groups. Doctor's delay in making the right diagnosis occurred in 60% of younger patients (≤40 years, n = 5), whereas among women aged 41-69years (n = 34) 50% suffered from psychiatric comorbidities. In patients ≥70 years (n = 28) social factors such as isolation, being widowed and living in a retirement home were present in most of the cases. Delay in seeking medical care was also associated with increasing age. Across all age groups, coping factors such as denial and indifference were also associated with an increase in the odds of delayed presentation, as opposed to fear. CONCLUSIONS: Factors possibly explaining late medical consultation seem to differ according to age. Psychological factors are crucial in patients' delay whereas age and social factors are relevant in doctors' and system's delay.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Diagnóstico Tardio/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adaptação Psicológica , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento
15.
Proteomics ; 15(2-3): 365-73, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25311472

RESUMO

Epithelial ovarian carcinoma (EOC) is a deadly disease, with a 5-year survival of 30%. The aim of the study was to perform broad-scale protein signaling activation mapping to evaluate if EOC can be redefined based on activated protein signaling network architecture rather than histology. Tumor cells were isolated using laser capture microdissection (LCM) from 72 EOCs. Tumors were classified as serous (n = 38), endometrioid (n = 13), mixed (n = 8), clear cell (CCC; n = 7), and others (n = 6). LCM tumor cells were lysed and subjected to reverse-phase protein microarray to measure the expression/activation level of 117 protein drug targets. Unsupervised hierarchical clustering analysis was utilized to explore the overall signaling network. ANOVA was used to detect significant differences among the groups (p < 0.05). Regardless of histology, unsupervised analysis revealed five pathway-driven clusters. When the EOC histotypes were compared by ANOVA, only CCC showed a distinct signaling network, with activation of EGFR, Syk, HER2/ErbB2, and SHP2 (p = 0.0007, p = 0.0021, p < 0.0001, and p = 0.0410, respectively). The histological classification of EOC fails to adequately describe the underpinning protein signaling network. Nevertheless, CCC presents unique signaling characteristics compared to the other histotypes. EOC may need to be characterized by functional signaling activation mapping rather than pure histology.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Mapas de Interação de Proteínas , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Receptores ErbB/análise , Receptores ErbB/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Medicina de Precisão , Análise Serial de Proteínas , Proteína Tirosina Fosfatase não Receptora Tipo 11/análise , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteínas Tirosina Quinases/análise , Proteínas Tirosina Quinases/metabolismo , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Quinase Syk , Adulto Jovem
16.
AAPS J ; 12(4): 504-18, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20549403

RESUMO

Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology.


Assuntos
Biomarcadores Tumorais/metabolismo , Nanopartículas , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias da Próstata/metabolismo , Proteoma , Sequência de Aminoácidos , Cromatografia em Gel , Diagnóstico Precoce , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Proteínas de Neoplasias/química , Neoplasias Ovarianas/diagnóstico , Mapeamento de Peptídeos , Neoplasias da Próstata/diagnóstico , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
17.
PLoS One ; 4(10): e7670, 2009 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-19888321

RESUMO

BACKGROUND: Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS: Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS: S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers.


Assuntos
Biomarcadores Tumorais , Proteínas de Ciclo Celular/sangue , Regulação Neoplásica da Expressão Gênica , Espectrometria de Massas/métodos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Proteômica/métodos , Proteínas S100/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Transplante de Neoplasias , Proteína A6 Ligante de Cálcio S100
18.
Mol Diagn Ther ; 13(5): 297-311, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19791834

RESUMO

As recent scientific findings using whole-genome mutational scanning technologies have concluded, cancer is a protein pathway disease, which is often diagnosed too late, when the success of therapeutic modalities is very limited. Proteomics has been proposed as the field that can help overcome this limitation and usher in a new era of molecular investigation for early diagnosis and classification of tumors. Proteomics applications in cancer research encompass two general aspects: (i) the study and characterization of protein production; and (ii) the definition of protein function. The first aims to identify qualitative or quantitative differences in the proteome that can help differentiate between healthy and diseased states or achieve a better clinical classification of diseases. The second studies the complexity of protein interactions and their activation states, mapping the network of signaling pathways within and outside the cells. The challenges in translating the findings of proteomics research into clinical practice are numerous. Lack of reproducibility, variable availability of samples and the bias associated with their selection and handling, the need for large, prospective validation trials, and finally the strict requirement for a very high level of clinical sensitivity and specificity are some of the hurdles that need to be overcome to achieve early detection and treatment. Nevertheless, proteomics is a field in rapid progression that has already developed beyond initial criticism and is making its way toward important applications and discoveries. Specifically, there has been an increasing number of reports on the potential clinical application of proteomics for early detection as well as risk assessment and management of ovarian cancer. This disease is the leading cause of death from gynecologic malignancies in the US, with poor prognosis resulting from the lack of reliable, sensitive screening tests and the limited understanding of the mechanisms of chemoresistance and relapse. In the future, serum proteomics applications in the gynecologic oncology field could identify blood-based biomarkers that are predictors of disease presence or progression, and tissue proteomics could help define the optimal targeted agent and effective dose for each patient's disease. These advances will allow improved monitoring of therapy response and disease relapse, and aid in the engineering of new drugs and strategies to circumvent resistance mechanisms while avoiding the adverse effects of traditional chemotherapy.


Assuntos
Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/terapia , Proteômica/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo
19.
Nano Res ; 1(6): 502-518, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20467576

RESUMO

Urine is a potential source of diagnostic biomarkers for detection of diseases, and is a very attractive means of non-invasive biospecimen collection. Nonetheless, proteomic measurement in urine is very challenging because diagnostic biomarkers exist in very low concentration (usually below the sensitivity of common immunoassays) and may be subject to rapid degradation. Hydrogel nanoparticles functionalized with Cibacron Blue F3G-A (CB) have been applied to address these challenges for urine biomarker measurement. We chose one of the most difficult low abundance, but medically relevant, hormones in the urine: human growth hormone (hGH). The normal range of hGH in serum is 1 to 10 ng/mL but the urine concentration is suspected to be a thousand times less, well below the detection limit (50 pg/mL) of sensitive clinical hGH immunoassays. We demonstrate that CB particles can capture, preserve and concentrate hGH in urine at physiological salt and urea concentrations, so that hGH can be measured in the linear range of a clinical immunometric assay. Recombinant and cadaveric hGH were captured from synthetic and human urine, concentrated and measured with an Immulite chemiluminescent immunoassay. Values of hGH less than 0.05 ng/mL (the Immulite detection limit) were concentrated to 2 ng/mL, with a urine volume of 1 mL. Dose response studies using 10 mL of urine demonstrated that the concentration of hGH in the particle eluate was linearly dependent on the concentration of hGH in the starting solution, and that all hGH was removed from solution. Thus if the starting urine volume is 100 mL, the detection limit will be 0.1 pg/mL. Urine from a healthy donor whose serum hGH concentration was 1.34 ng/mL was studied in order detect endogenous hGH. Starting from a volume of 33 mL, the particle eluate had an hGH concentration of 58 pg/mL, giving an estimated initial concentration of hGH in urine of 0.175 pg/mL. The nanotechnology described here appears to have the desired precision, accuracy and sensitivity to support large scale clinical studies of urine hGH levels.

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