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1.
Future Oncol ; 12(17): 2001-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27255717

RESUMO

AIM: To shed light on the clinical role of HER2 status in serum as extracellular domain (ECD) and corresponding circulating tumor cells (CTCs) in metastatic breast cancer patients. METHODS: 68 patients were analyzed. Serum HER2 was determined by ADVIA Centaur(®) Serum HER2 test. CellSearch System was performed for CTC quantification. RESULTS: HER2 was overexpressed in 21 primary tumors. In total, 19 patients had ECD >15 ng/ml (the cut-off used), 48 patients had at least one CTC. ECD positivity was associated with CTC number (p = 0.01), HER2-positive CTC (p = 0.01) and the ratio HER2-positive CTC/total CTC (p = 0.02). ECD was not associated with survival. CONCLUSION: ECD in combination with HER2 CTC status would deserve further investigation in larger series for addressing its putative prognostic relevance.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Receptor ErbB-2/sangue , Adulto , Idoso , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Espaço Extracelular , Feminino , Humanos , Imunoensaio , Estimativa de Kaplan-Meier , Medições Luminescentes , Pessoa de Meia-Idade
2.
Tumour Biol ; 36(2): 991-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25318603

RESUMO

Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45%) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8%, p = 0.038). CTCs were found in 45% of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.


Assuntos
Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/cirurgia , Prognóstico
3.
Lancet Oncol ; 15(4): 406-14, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24636208

RESUMO

BACKGROUND: We aimed to assess the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with metastatic breast cancer by undertaking a pooled analysis of individual patient data. METHODS: We contacted 51 European centres and asked them to provide reported and unreported anonymised data for individual patients with metastatic breast cancer who participated in studies between January, 2003, and July, 2012. Eligible studies had participants starting a new line of therapy, data for progression-free survival or overall survival, or both, and CTC quantification by the CellSearch method at baseline (before start of new treatment). We used Cox regression models, stratified by study, to establish the association between CTC count and progression-free survival and overall survival. We used the landmark method to assess the prognostic value of CTC and serum marker changes during treatment. We assessed the added value of CTCs or serum markers to prognostic clinicopathological models in a resampling procedure using likelihood ratio (LR) χ(2) statistics. FINDINGS: 17 centres provided data for 1944 eligible patients from 20 studies. 911 patients (46·9%) had a CTC count of 5 per 7·5 mL or higher at baseline, which was associated with decreased progression-free survival (hazard ratio [HR] 1·92, 95% CI 1·73-2·14, p<0·0001) and overall survival (HR 2·78, 95% CI 2·42-3·19, p<0·0001) compared with patients with a CTC count of less than 5 per 7·5 mL at baseline. Increased CTC counts 3-5 weeks after start of treatment, adjusted for CTC count at baseline, were associated with shortened progression-free survival (HR 1·85, 95% CI 1·48-2·32, p<0·0001) and overall survival (HR 2·26, 95% CI 1·68-3·03) as were increased CTC counts after 6-8 weeks (progression-free survival HR 2·20, 95% CI 1·66-2·90, p<0·0001; overall survival HR 2·91, 95% CI 2·01-4·23, p<0·0001). Survival prediction was significantly improved by addition of baseline CTC count to the clinicopathological models (progression-free survival LR 38·4, 95% CI 21·9-60·3, p<0·0001; overall survival LR 64·9, 95% CI 41·3-93·4, p<0·0001). This model was further improved by addition of CTC change at 3-5 weeks (progression-free survival LR 8·2, 95% CI 0·78-20·4, p=0·004; overall survival LR 11·5, 95% CI 2·6-25·1, p=0·0007) and at 6-8 weeks (progression-free survival LR 15·3, 95% CI 5·2-28·3; overall survival LR 14·6, 95% CI 4·0-30·6; both p<0·0001). Carcinoembryonic antigen and cancer antigen 15-3 concentrations at baseline and during therapy did not add significant information to the best baseline model. INTERPRETATION: These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival. CTC count also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not. FUNDING: Janssen Diagnostics, the Nuovo-Soldati foundation for cancer research.


Assuntos
Neoplasias da Mama/secundário , Células Neoplásicas Circulantes/patologia , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Antígeno Carcinoembrionário/sangue , Contagem de Células , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Estimativa de Kaplan-Meier , Funções Verossimilhança , Pessoa de Meia-Idade , Mucina-1/sangue , Células Neoplásicas Circulantes/metabolismo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
4.
Breast Cancer Res ; 16(2): R43, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24758318

RESUMO

INTRODUCTION: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. METHODS: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. RESULTS: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90). CONCLUSIONS: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.


Assuntos
Neoplasias da Mama/patologia , Contagem de Células/instrumentação , Oncologia/instrumentação , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Contagem de Células/normas , Feminino , Humanos , Cooperação Internacional , Laboratórios/normas , Oncologia/normas , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/metabolismo , Padrões de Referência , Reprodutibilidade dos Testes
5.
Int J Colorectal Dis ; 29(9): 1053-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25008360

RESUMO

PURPOSE: Circulating tumor cells (CTCs) represent an independent prognostic factor in metastatic colorectal cancer, while their significance in early stages is still an open issue. The aim of the study is to investigate the role of CTCs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CT-RT). METHODS: In this prospective single institutional study, cT3-4 and/or N+ rectal cancer was treated with neoadjuvant CT-RT. The primary endpoints were as follows: evaluation of CTCs at baseline (t0), after CT-RT (t1), within 7 days after surgery (t2), and at 6 months from surgery (t3) and correlation with main patient/tumor characteristics, CEA, response to neoadjuvant therapy, and disease-free survival (DFS). CTCs were enumerated with the CellSearch System in 22.5 ml peripheral blood. A repeated measure analysis for binary outcome was used to evaluate over time changes in the percentage of CTCs detectable in blood samples. RESULTS: Of the 90 patients enrolled in this study, 85 were eligible consisting of 52 males and 33 females. Median age was 63 years and median follow-up was 38 months. CTCs were available for all patients at t0, for 67 at t1, for 68 at t2, and for 62 at t3. CTCs >0 were reported on 16 (19%) at t0, on 5 (7.5%) at t1, on 6 (9%) at t2, and on 3 (5%) at t3 (P value for trend 0.039). Only for CT-RT responders, CTCs reduced from t0 to t1. No statistically significant association was found between CTCs and main patient/tumor characteristics and DFS. CONCLUSIONS: Sixteen patients (19%) had CTCs ≥1 at t0 with reduction in CTC number in case of objective remissions. The proportion of patients with CTCs ≥1 decreased over the time as the therapeutic course proceeded. Much effort should be oriented toward increasing CTC detection rate by enhancing technical tests and achieving better patient characterization.


Assuntos
Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Células Neoplásicas Circulantes/metabolismo , Neoplasias Retais/sangue , Neoplasias Retais/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de Sobrevida
6.
Scand J Clin Lab Invest ; 74(5): 385-91, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24693994

RESUMO

The serial monitoring of cardiac troponin represents an effective approach for the early identification, assessment, and monitoring of chemotherapy-induced cardiac injury. Over the last few years new generations of troponin assays, referred to as sensitive and high sensitivity assays, able to detect very low concentrations of troponin, have been progressively released on different platforms. Some studies have assessed the comparability of the cTnI measurements with the new assays versus the conventional ones, but none of these in the oncological population. We compared the cTnI results determined on Stratus CS and ADVIA Centaur CP System in 70 breast cancer patients, for a total of 327 samples collected during different cycles of treatment. Correlation (Spearman = 0.732) and agreement (91.4%) between the assays were good (244 concordant negatives and 55 concordant positives), with a frequency of 8.6% discordant results among the cTnI measurements. Despite the well-known lack in the harmonization and standardization of the currently commercially available cTnI methods, we found a good clinical concordance of cTnI determination on both systems.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/sangue , Doenças Cardiovasculares/sangue , Troponina I/sangue , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Análise Química do Sangue , Neoplasias da Mama/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos
7.
J Clin Med ; 12(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37373727

RESUMO

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles' cytologic yields. MATERIAL: A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. RESULTS: A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4-97.1%) for the 19-G needle and 92.6% (CI: 86.3-96.5%) for the 22-G needle (p = 0.80). The percentage of malignant cells in the cell block was 63.9% and 61.5% for the 22-G and 19-G needles, respectively. The cell count assessed by flow cytometry was 2071 cells/µL (IQR: 600,2265) with the 22-G needle and 2761 cells/µL (IQR: 505,3250) with the 19-G needle (p = 0.79). The malignant cell count was 0.05 × 103 cells/µL with the 22-G and 0.08 × 103 cells/µL with the 19-G needle (p = 0.70). There was no difference in the presence of tissue cores in the samples, and rapid on-site evaluation (ROSE) cellularity was comparable between the two needles. CONCLUSIONS: The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for cyto-histological evaluation of hilar and mediastinal lymphadenopathies. There is no difference between the 19-G and 22-G needle cell counts evaluated by flow cytometry.

8.
J Cancer Surviv ; 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37418169

RESUMO

PURPOSE: This study aimed to test the efficacy of a 6-month intervention on weight loss in a group of overweight or obese breast cancer (BC) survivors. We promoted adherence to a healthy diet or/and to increase physical activity, making use of a step counter device. Here we present results regarding the change in anthropometric measures and blood parameters. METHODS: 266 women treated for BC with a BMI ≥ 25 kg/m2 were randomized to a 6-month intervention into four arms: Dietary Intervention (DI); Physical Activity Intervention (PAI); Physical Activity and Dietary Intervention (PADI); Minimal Intervention (MI). Women were offered individualized counseling by a dietitian, a physiotherapist and a psychologist. Participants were followed up for an additional 18 months. RESULTS: 231 women completed the 6-month intervention and 167 completed the additional 18-month follow-up. Respectively, 37.5% and 36.7% of women included in the DI and PADI arm reached the objective of the trial (weight reduction > 5%). Significant weight and circumferences decrease was observed at 6-month in the four arms. Weight decrease was more pronounced in the DI (-4.7% ± 5.0%) and PADI (-3.9% ± 4.5%) arms, persisted over time (at 12 and 24 months), where counseling was mainly focused on the dietic component. The intervention had an effect on the glucose level with a significant reduction in whole population (-0.9 ± 11.7 p-value 0.02) and most pronounced in the PADI arm (-2.4 ± 7.8 p-value 0.03). CONCLUSIONS: Lifestyle intervention mainly focused on the dietetic component and making use of a step counter improved body weight, circumferences and glucose levels. IMPLICATIONS FOR CANCER SURVIVORS: A personalized approach yields a potential clinical benefit for BC survivors.

9.
Cancers (Basel) ; 14(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36291788

RESUMO

BACKGROUND: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. METHODS: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. RESULTS: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells' increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). CONCLUSIONS: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure.

10.
Cancers (Basel) ; 14(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36139632

RESUMO

BACKGROUND: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. METHODS: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. RESULTS: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. CONCLUSION: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments.

11.
Breast Cancer Res Treat ; 122(1): 211-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19967556

RESUMO

Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (P-value < 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Modelos Biológicos , Células Neoplásicas Circulantes , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/sangue , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Contagem de Células , Progressão da Doença , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Risco
12.
Ann Surg Oncol ; 17(6): 1539-45, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20135356

RESUMO

BACKGROUND: Few data exist on the potential role of circulating tumor cells (CTCs) in patients with operable breast cancer. If the presence of CTCs in early breast cancer could predict an increased risk for relapse, it might be an early marker for treatment efficacy and could help in deciding treatment continuation. METHODS: Thirty milliliters of peripheral blood was taken from 56 breast cancer patients before surgery and again 5 days after surgery, and the presence of CTCs was evaluated. In case of positivity of one of the perioperative samples, another sample was taken after 30 days. The presence of CTCs was assessed with the CellSearch System (Veridex, Warren, NJ). RESULTS: One to three CTCs were found in 16 (29%) of 56 patients before surgery, in 14 (30%) of 47 patients at day 5, and in 8 (30%) of 27 at day 30. No association with pathological characteristics was found, apart a borderline significant association between presence of CTCs at baseline and vascular invasion (P = 0.07). When we looked at concordance between CTCs at baseline and after day 5 (47 patients), we found 40% discordant samples (10 negative at baseline and positive at day 5, and 9 vice versa). CONCLUSIONS: This study provides evidence of the presence of CTCs in approximately 30% of patients with localized breast cancer both before and after surgery, with change from positive to negative and vice versa in 40% of cases. No association with the pathological variables was found, except for vascular invasion and presence of preoperative CTCs. Long-term follow-up will be required to understand the significance of these data.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Células Neoplásicas Circulantes , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Resultado do Tratamento
13.
Biomarkers ; 15(3): 259-65, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20030573

RESUMO

Postoperative atrial fibrillation (AF) is a well-known complication occurring after thoracic surgery. B-type natriuretic peptide has recently been investigated as a predictive marker of postoperative AF after cardiac surgery. The aim of this study was to evaluate a definite cut-off for N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting postoperative AF in lung cancer patients. NT-proBNP was determined before and after surgery in 400 patients. Cardiac function was monitored by continuous postoperative ECG and clinical cardiological evaluation. AF occurred in 18% of the patients. Receiver operating characteristic curve analyses identified a cut-off of 182.3 ng l(-1) as the one with the highest sensitivity and specificity. Perioperative increased levels of NT-proBNP seem to predict postoperative AF in patients undergoing thoracic surgery, and a single cut-off of 182.3 ng l(-1) can be used to select high-risk patients who could receive preventive therapy, leading to a considerable decrease in the total costs associated with the management of this complication.


Assuntos
Fibrilação Atrial/patologia , Neoplasias Pulmonares/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Área Sob a Curva , Biomarcadores/sangue , Eletrocardiografia/métodos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Curva ROC , Risco , Sensibilidade e Especificidade
14.
J Med Virol ; 81(2): 271-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19107962

RESUMO

Human papillomavirus (HPV) are distributed widely and persistent infection with high-risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR-HPV genotypes in 199 women with cervical pre-invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR-HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR-HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR-HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found.


Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , DNA Viral/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
15.
Oncology ; 77(6): 358-65, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20068365

RESUMO

BACKGROUND: alpha-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. PATIENTS AND METHODS: In a randomized phase II trial to assess tolerability and safety, we assigned patients with advanced slow-growing solid tumours to 1 of 6 two- or three-drug combinations: alpha-interferon 0.5 million IU b.i.d., thalidomide (100 mg b.i.d. reduced to 100 mg daily), or celecoxib (400 mg daily reduced to 200 mg). Circulating endothelial cells and progenitors (CECs, CEPs) and vascular endothelial growth factor were also studied. RESULTS: From January 2002 to September 2005, 62 patients were enrolled. Four months after initiating treatment, 3 (4%) had partial response, 40 (64%) had stable disease and 19 (30%) had disease progression. Median duration of clinical benefit (partial response/stable disease) was 11.3 months. Patients receiving a third drug had significantly less stable disease plus partial response (chi(2) test, p = 0.002) than those receiving two drugs. The treatments were generally well tolerated, but neurotoxicity (G3 lethargy) occurred in 6 patients. Baseline CEPs were lower (p = 0.004) in patients with clinical benefit at 6 months than those without benefit. After 2 months of treatment CECs were lower than at baseline (p = 0.018) in patients without clinical benefit, and CEPs were higher than at baseline (p = 0.003) in patients with benefit. CONCLUSIONS: In pretreated patients with advanced slow-growing solid tumours, long-term metronomic administration of two-drug combinations of alpha-interferon, thalidomide or celecoxib was well tolerated and had antitumour activity. Low baseline CEPs in patients with subsequent clinical benefit suggest that CEC count may identify patients likely to benefit from long-term metronomic anti-angiogenic treatment.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Humanos , Neoplasias/irrigação sanguínea , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue
16.
Crit Rev Oncol Hematol ; 134: 39-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30771872

RESUMO

BACKGROUND: The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease. METHODS: In a retrospective, pooled analysis of individual patient data from 18 cohorts, including 2436 MBC patients, a CTC threshold of 5 cells per 7.5 ml was used for stratification based on molecular subtypes, disease location, and prior treatments. Patients with ≥ 5 CTCs were classified as Stage IVaggressive, those with < 5 CTCs as Stage IVindolent. Survival was analyzed using Kaplan-Meier curves and the log rank test. RESULTS: For all patients, Stage IVindolent patients had longer median overall survival than those with Stage IVaggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IVindolent vs. 18.7 months Stage IVaggressive, p < 0.0001). Moreover, patients with Stage IVindolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location. CONCLUSIONS: We confirm the identification of two subgroups of MBC, Stage IVindolent and Stage IVaggressive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Estadiamento de Neoplasias/normas , Células Neoplásicas Circulantes/patologia , Seleção de Pacientes , Consenso , Prova Pericial , Feminino , Humanos , Agências Internacionais
17.
Anticancer Res ; 28(5B): 3061-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19031957

RESUMO

BACKGROUND: The diagnostic utility of procalcitonin (PCT) and C-reactive protein (CRP) to discriminate between infective fever and fever due to inflammation was assessed in hemato-oncological patients treated with aggressive chemotherapy. PATIENTS AND METHODS: Values of PCT and PCR measured on days -1, 0, 1, 3 and 5 of onset of fever were analyzed using longitudinal regression analysis. Of 236 febrile episodes in 166 patients, 39 were due to bacteremia, 62 to other infections and 135 were classified as fever of unknown origin. RESULTS: PCT concentration increased early only in bacteremia and other infections (p<0.001), with the highest levels at day +1. No different trends were noted in patients with low WBC count (<1,000/microl). CRP increased with a similar trend in all the three groups. CONCLUSION: PCT determination may contribute significantly to the management of hemato-oncological patients who experience febrile episodes.


Assuntos
Bacteriemia/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Febre/sangue , Neoplasias/sangue , Precursores de Proteínas/sangue , Adolescente , Adulto , Idoso , Bacteriemia/complicações , Bacteriemia/microbiologia , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Febre/complicações , Febre/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/complicações , Cocos Gram-Positivos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/microbiologia , Adulto Jovem
18.
Anticancer Res ; 24(2C): 1261-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15154657

RESUMO

BACKGROUND: The proto-oncogene HER2/neu encodes for a transmembrane receptor protein whose overexpression in breast cancer may be associated with poor prognosis. Its extracellular domain (HER2 ECD) can be shed into the circulation. The purpose of this study was to evaluate the predictive value of HER2 ECD in patients with advanced breast cancer. PATIENTS AND METHODS: HER2 ECD was determined in 39 patients with advanced breast cancer, treated with oral cyclophosphamide and methotrexate (CM) at low doses. HER2 ECD levels were determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of chemotherapy, when all the patients were re-evaluated. RESULTS: Based on the response to chemotherapy, the patients were divided into two groups: progressive disease (PD, 14 patients) and patients with clinical benefit (CB; i.e. patients with stable or responsive disease, 25 patients). The patients with PD had a mean baseline value of HER2 ECD of 38.3+/-69.2 ng/ml, while the group of CB showed lower levels (9.2+/-2.3 ng/ml, p<0.05). After 2 months, the mean value of HER2 ECD in the PD group increased to 71.6+/-146 ng/ml, while in the other group the levels did not change (9.7+/-2.4 ng/ml). At follow-up, significant differences were noted in both the time to progression and overall survival, with patients with increased levels of HER2 ECD at baseline (> or = 15 ng/ml) showing a worse clinical outcome. CONCLUSION: Increased pretreatment levels of HER2 ECD identify a subset of patients with more aggressive tumors and less response to CM chemotherapy. During therapy, increasing levels of HER2 ECD are associated with disease progression.


Assuntos
Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/sangue , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estrutura Terciária de Proteína , Proto-Oncogene Mas
19.
EMBO Mol Med ; 6(11): 1371-86, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25358515

RESUMO

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of > 90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance.


Assuntos
Neoplasias da Mama/diagnóstico , Genômica/métodos , Células Neoplásicas Circulantes/patologia , Patologia Molecular/métodos , Análise de Célula Única/métodos , Feminino , Humanos
20.
Int J Biol Markers ; 28(3): 313-7, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-23722302

RESUMO

Since squamous cell carcinoma antigen (SCC-Ag) testing became commercially available on the Architect platform, the previously established method on the Abbott IMx platform has been progressively replaced. Aim of this work was to compare SCC-Ag values obtained with the 2 methods. Clinical and laboratory data of 188 patients for whom SCC-Ag determination was requested, were reviewed. IMx was used to determine the levels of SCC-Ag from June 2007 to May 2009, while the Architect system was used from June 2009 to April 2011. Only patients consistently diagnosed with no evidence of disease, for whom at least 2 determinations with each analyzer were available were used. Comparison of the results obtained with the 2 systems was then performed. Mean values for SCC-Ag were 0.56 ng/mL (Standard Error (SE): 0.08) with the IMx method, and 1.08 ng/mL (SE 0.10) with Architect (p<0.0001). False positive results were found in 4.8% of patients with the IMx method and in 9.5% of patients with Architect (p=0.049). The values of SCC-Ag determined on the Architect platform are higher than those obtained on the IMx, with a higher percentage of false positive results.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Serpinas/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias do Colo do Útero/patologia
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