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1.
Medicine (Baltimore) ; 100(6): e24640, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578585

RESUMO

ABSTRACT: Lung cancer is the most common type of cancer worldwide with a high mortality rate. The specific tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR) have made enormous strides in non-small-cell lung cancer (NSCLC) treatment. The novel systemic immune-inflammation index (SII), a parameter that integrates lymphocytes, neutrophils, and platelets, has been found to play the vital role of a marker for predicting survival and recrudescence in various tumors.We retrospectively examined 102 patients with different EGFR-mutant lung adenocarcinomas. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. Cut-off points were identified using the receiver operating characteristic curves with the maximum log-rank values. The Cox proportional hazards regression, expressed as p value, hazards regression, and 95% confidence interval, was conducted to assess the prognostic values of variables in overall survival (OS)/ progression-free survival (PFS).Lower SII was associated with prolonged survival in patients with different EGFR mutant lung adenocarcinomas in both variable and multivariable analyses.SII before treatment was a powerful indicator for the PFS and OS of patients who received the first-generation EGFR-TKI.


Assuntos
Adenocarcinoma/mortalidade , Inflamação , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/mortalidade , Índice de Gravidade de Doença , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , China , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
2.
Am J Surg ; 221(1): 162-167, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32746979

RESUMO

BACKGROUND: Chronic kidney disease (CKD) can increase serum carcinoembryonic antigen (CEA) levels. We thus aimed to evaluate the impact of CKD on CEA prognostic accuracy in colorectal cancer. METHODS: Altogether, 429 patients who underwent curative resection for stages I-III colorectal adenocarcinoma were grouped according to postoperative CEA levels and history of CKD. RESULTS: Three-year disease-free survival (DFS) was higher in patients with normal postoperative CEA (group A, 83.4%) than in those with elevated postoperative CEA (group B, 64.3%) (p < 0.001). CKD patients had higher postoperative CEA levels than non-CKD patients (odds ratio 3.27, 95% confidence interval 1.78-5.99, p < 0.001). In multivariable analysis, postoperative CEA level was an independent prognostic factor for DFS in non-CKD, but not CKD, patients. CONCLUSIONS: CKD can increase postoperative CEA levels in colorectal cancer patients. Elevated postoperative CEA levels were associated with shorter DFS in non-CKD, but not CKD, patients.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
3.
Anticancer Res ; 40(10): 5679-5685, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988893

RESUMO

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Esofágicas/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/patologia , Contagem de Células , Separação Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Prognóstico
4.
J Stroke Cerebrovasc Dis ; 29(9): 104891, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807409

RESUMO

PURPOSE: We summarized the clinical manifestations, laboratory data, and brain MRI of patients with Trousseau syndrome related cerebral infarction and compared them to patients with other types of cerebral infarction. Through our present research, we hope to aid the neurologists in recognizing and diagnosing this syndrome. METHODS: A total of 31 patients at our institution were identified with cerebral infarction resulting from Trousseau syndrome. We have also selected the 180 patients who have suffered from cerebral infarction as control groups and these patients were distributed to large-artery atherosclerosis group; cardio-embolism group; small-artery occlusion group, according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The clinical data and neuroimage of these patients were collected. RESULTS: All our 31 cancer patients were confirmed by pathological biopsy to be adenocarcinomas and the most common cancers are gastric and lung cancers. Patients with Trousseau syndrome exhibited high serum carbohydrate antigen CEA, CA 125 and CA 199 levels. Compared to patients with other types of cerebral infarction, patients with Trousseau syndrome had an increased severity and worse prognosis. Besides, patients had the highest mean level of plasma D-dimer. We also found multiple lesions in multiple vascular territories was the most frequent type of DWI patterns in patients of Trousseau syndrome. CONCLUSIONS: Trousseau syndrome can progress rapidly and become life-threatening. For patients who developed unexplained cerebral infarction involving multiple arterial territories, with elevated plasma D-dimer and cancer antigens, Trousseau syndrome should always be considered.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/sangue , Infarto Cerebral/diagnóstico , Imagem de Difusão por Ressonância Magnética , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infarto Cerebral/sangue , Infarto Cerebral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome , Trombose/sangue , Trombose/complicações , Regulação para Cima
5.
Actas urol. esp ; 44(6): 437-443, jul.-ago. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-199421

RESUMO

OBJETIVO: El objetivo del trabajo fue valorar la utilidad de la PET/TC con 18F-colina en pacientes con cáncer de próstata tratados con braquiterapia en recidiva bioquímica, así como valorar los cambios en el manejo terapéutico derivados de su resultado. MATERIAL Y MÉTODOS: Estudio retrospectivo en el que se incluyeron 20 pacientes entre 51 y 78 años, con antecedente de adenocarcinoma de próstata que habían sido tratados con braquiterapia, que presentaban recidiva bioquímica (PSA 3,1-12ng/ml) y estudio de extensión (TC y gammagrafía ósea) sin alteraciones. Los hallazgos visualizados en la PET/TC con 18F-colina fueron correlacionados con la histopatología y/o la evolución del PSA tras la terapia. RESULTADOS: En 15 pacientes la PET/TC con 18F-colina detectó únicamente recidiva local. En 4 pacientes recidiva local y linfática y en un1 paciente afectación local y ósea. La recidiva local detectada en la PET se confirmó anatomopatológicamente en el 85% de los casos. En un paciente los hallazgos visualizados en la PET resultaron ser una prostatitis y en otro paciente no se pudo confirmar. De los pacientes con recidiva local y linfática se confirmó histológicamente la recidiva local en 3 de 4. En el 25% de los pacientes la PET/TC con 18F-colina cambió el manejo terapéutico, desestimando la cirugía de rescate inicialmente prevista en 3 casos, en uno radioterapia y en otro la braquiterapia. CONCLUSIÓN: La PET/TC con 18F-colina podría ser una técnica útil en el grupo de pacientes tratados con braquiterapia con recidiva bioquímica, permitiendo localizar la afectación locorregional y a distancia no detectada con imágenes convencionales, determinando así un manejo terapéutico más adecuado


OBJECTIVE: The objective of the study was to evaluate the usefulness of 18F-choline PET/CT in biochemically recurrent prostate cancer patients treated with brachytherapy, as well as to assess the changes in therapeutic management derived from its outcome. MATERIAL AND METHODS: Retrospective study of 20 patients between 51 and 78 years old, with a history of prostate adenocarcinoma that had been treated with brachytherapy and presented biochemical recurrence (PSA 3.1-12 ng/ml) and staging tests (CT and bone scan) without alterations, were included. The findings visualized in the PET/CT scan with 18F-choline were correlated with the histopathology and/or the evolution of the PSA after therapy. RESULTS: 18F-choline PET/CT scan only detected local recurrence in 15 patients. Local and regional recurrences were seen in 4 patients, and 1 patient presented local and bone recurrence. Local recurrence detected in PET was confirmed by anatomopathological studies in 85% of the cases. In one patient, these findings (PET scan) turned out to be prostatitis, and it could not be confirmed in another patient. Of the cases with local and regional recurrence, local recurrence was histologically confirmed in 3 out of 4 patients. 18F-choline PET/CT changed the therapeutic management in 25% of the patients, discarding the initially planned salvage surgery in 3 cases, 1 radiotherapy and 1 brachytherapy. CONCLUSION: 18F-choline PET/CT could be a useful technique in the group of patients with biochemical recurrence after brachytherapy, providing locoregional and distant involvement findings which had not been detected with conventional imaging tests, thus determining a more adequate therapeutic management


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Braquiterapia , Colina/análogos & derivados , Tomografia Computadorizada por Raios X/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Adenocarcinoma/sangue , Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/sangue , Recidiva Local de Neoplasia/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos
6.
Zhonghua Wai Ke Za Zhi ; 58(7): 505-511, 2020 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-32610419

RESUMO

Objective: To compare the short-term outcomes and long-term survivals of radical antegrade modular pancreatosplenectomy(RAMPS) and conventional distal pancreatectomy(CDP). Methods: A total of consecutive 304 patients including 176 male patients and 128 female patients who underwent RAMPS or CDP at Pancreas Center, the First Affiliated Hospital with Nanjing Medical University from May 2013 to June 2019 were retrospectively analyzed. The median age was 64.1 years old (range:39 to 85 years old). There were 101 patients underwent RAMPS and 203 patients underwent CDP. Measurement data with skewed distribution were presented as (M(Q(R))) and comparison between groups was evaluated with the Wilcoxon rank sum test. Count data were analyzed using the χ(2) test or Fisher exact probability. Survival analyses were performed by the Kaplan-Meier method after a one to one propensity score matching(PSM) conducted to balance several variables. Results: An eighty-one to eighty-one patients were enrolled after PSM. The overall morbidity was 32.1%(26/81)and there were no in-hospital mortalities in RAMPS. The median operative time was 225(95)minutes in RAMPS, not significantly longer as compared with CDP(210(130)minutes, P=0.916). The median greatest tumor diameter in RAMPS was 4.0(2.3)cm, not significantly larger as compared with CDP(4.5(2.2)cm, P=0.520).There were 34.6%(28/81)patients who presented with T4 tumors by 8(th) AJCC TNM staging system in RAMPS, which was not significantly different as compared with CDP(39.5%, χ(2)=0.574, P=0.902). The median number of examined lymph nodes was 9(9), not significantly greater in RAMPS as compared with CDP(10(11), P=0.992). The rate of negative posterior margins using 1 mm rule in RAMPS was 70.3%(52/74), significantly higher as compared with CDP(53.6%(30/56), χ(2)=3.817, P=0.044). The overall R0 resection rate was 44.6% (33/74) in RAMPS and 37.5% (21/56) in CDP, which was not significantly different(χ(2)=0.663, P=0.474). The median overall survival was 16.5 months for RAMPS, 25.2 months for CDP, and there was no statistical difference between two groups(P=0.981). The median overall survival was 16.0 months for patients with preoperative CA19-9≥300 U/ml who underwent RAMPS, 10.1 months for patients who underwent CDP, without significant difference(P=0.082). Conclusions: RAMPS can improve the rate of negative posterior margins by 1 mm rule and probably increase R0 resection rate and the harvest of lymph nodes. RAMPS may be beneficial to some patients with preoperative CA19-9≥300 U/ml.


Assuntos
Adenocarcinoma/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Esplenectomia/métodos , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/sangue , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
PLoS One ; 15(6): e0233443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497056

RESUMO

Large (> 1 µm) tumor-derived extracellular vesicles (tdEVs) enriched from the cell fraction of centrifuged whole blood are prognostic in metastatic castration-resistant prostate cancer (mCRPC) patients. However, the highest concentration of tdEVs is expected in the cell-free plasma fraction. In this pilot study, we determine whether mCRPC patients can be discriminated from healthy controls based on detection of tdEVs (< 1µm, EpCAM+) and/or other EVs, in cell-free plasma and/or urine. The presence of marker+ EVs in plasma and urine samples from mCRPC patients (n = 5) and healthy controls (n = 5) was determined by flow cytometry (FCM) and surface plasmon resonance imaging (SPRi) using an antibody panel and lactadherin. For FCM, the concentrations of marker positive (+) particles and EVs (refractive index <1.42) were determined. Only the lactadherin+ particle and EV concentration in plasma measured by FCM differed significantly between patients and controls (p = 0.017). All other markers did not result in signals exceeding the background on both FCM and SPRi, or did not differ significantly between patients and controls. In conclusion, no difference was found between patients and controls based on the detection of tdEVs. For FCM, the measured sample volumes are too small to detect tdEVs. For SPRi, the concentration of tdEVs is probably too low to be detected. Thus, to detect tdEVs in cell-free plasma and/or urine, EV enrichment and/or concentration is required. Furthermore, we recommend testing other markers and/or a combination of markers to discriminate mCRPC patients from healthy controls.


Assuntos
Adenocarcinoma/secundário , Vesículas Extracelulares/metabolismo , Citometria de Fluxo/métodos , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/urina , Ressonância de Plasmônio de Superfície/métodos , Adenocarcinoma/sangue , Adenocarcinoma/urina , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/sangue , Biomarcadores Tumorais , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Vesículas Extracelulares/química , Humanos , Masculino , Proteínas do Leite/sangue , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/urina , Projetos Piloto , Neoplasias de Próstata Resistentes à Castração/patologia
8.
PLoS One ; 15(6): e0233687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502149

RESUMO

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.


Assuntos
Adenocarcinoma/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Fumar Tabaco/sangue , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
N Engl J Med ; 382(23): 2187-2196, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32469183

RESUMO

BACKGROUND: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Leuprolida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Pirimidinonas/uso terapêutico , Testosterona/sangue , Adenocarcinoma/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Injeções Subcutâneas , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Neoplasias da Próstata/sangue , Pirimidinonas/efeitos adversos
10.
J Cancer Res Ther ; 16(1): 127-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362622

RESUMO

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). Materials and Methods: Peripheral blood of histopathologically proven cases of lung AC and SCC was collected and processed for the isolation of miRNAs using commercially available kit. Primers against mir-2114, mir-2115, mir-2116, mir-2117, mir-449c, and mir-548q with loading control Caenorhabditis elegans were used. Screening was carried out in thirty cases of both AC and SCC, whereas twenty healthy controls were included. Results: Real-time polymerase chain reaction data revealed that the expression of mir-2114 and mir-449c in AC and mir-2115 in SCC was significantly upregulated. The expression of these miRNAs was also confirmed in lung AC cell line. The differential pattern of expression of these miRNAs can be used for precise diagnosis of lung carcinoma. Conclusions: We have used a noninvasive technique to identify the subtype of lung cancer based on molecular genetic signatures. The results suggest that through molecular profiling of miRNA, we can screen high-risk cases for cancer interception.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , MicroRNA Circulante/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/genética , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Prognóstico
11.
Eur J Cancer ; 133: 66-73, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32446145

RESUMO

BACKGROUND: Free triiodothyronine (FT3)/free thyroxine (FT4) ratio is an index estimating the peripheral activity of thyroid hormones. In a previous experience, we identified a prognostic role for FT3/FT4 ratio in chemorefractory patients treated with regorafenib. Therefore, we planned this post hoc analysis of the phase III CORRECT trial of regorafenib versus placebo. METHODS: Seven hundred fifty-eight out of 760 randomised patients (503 in the regorafenib and 255 in the placebo arm) were evaluable for the present analyses, based on availability of FT3 and FT4 baseline values. Co-primary objectives were to explore the predictive role of FT3/FT4 ratio in patients treated with regorafenib compared with placebo and to validate the prognostic value of FT3/FT4 ratio in the CORRECT trial. RESULTS: For patients randomised to regorafenib, median overall survival (OS) was 4.0, 7.5 and 9.8 months in low, intermediate and high FT3/FT4 ratio subgroups, respectively. Hazard ratio (HR) for OS was 0.40 (p < 0.0001) when comparing intermediate versus low and 0.32 (p < 0.0001) when comparing high versus low FT3/FT4 ratio. In the placebo arm, median OS was 3.3, 5.6 and 7.7 months, in the three subgroups. HR for OS was 0.47 (p < 0.0001) when comparing intermediate versus low and 0.33 (p < 0.0001) when comparing high versus low. FT3/FT4 ratio retained its association with OS in the multivariate model in both arms. CONCLUSIONS: While rejecting the predictive effect of baseline FT3/FT4 ratio, present data strengthen the prognostic role of the ratio, pave the way for direct clinical application, underline the need for a better biological understanding and suggest possible therapeutic implications for thyroid hormones.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Hormônios Tireóideos/sangue , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Testes de Função Tireóidea , Resultado do Tratamento
12.
J Cancer Res Clin Oncol ; 146(8): 1971-1978, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447484

RESUMO

PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.


Assuntos
Interleucina-10/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Feminino , Genótipo , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia
13.
PLoS One ; 15(4): e0231833, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298379

RESUMO

INTRODUCTION: Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies are diagnosis of EACs at an already advanced stage and distant metastases. Hence, we wanted to investigate the presence of systemic inflammatory interleukins (IL) and their impact on patient prognosis. MATERIAL AND METHODS: Systemic expression levels of pro- and anti-inflammatory markers (IL-2, IL-4, IL-6, IL-10, IL-17A and IL-22) in the sera of 43 EAC patients without neoadjuvant radiochemotherapy were measured by flow cytometric analysis. A correlation to clinicopathological data was performed. Log-rank and Cox regression analysis were used to investigate the impact on patient survival. 43 sera of age and gender matched healthy volunteers were used as controls. RESULTS: Increased systemic IL-6 (p = 0.044) and lower IL-17A (p = 0.002) levels were found in EAC patients as opposed to controls. A correlation of IL-10 levels with an increased T stage was found (p = 0.020). Also, systemic IL-10 levels were highly elevated in patients with distant metastasis (p<0.001). However, only systemic IL-17A levels had an influence on patient survival in multivariate analysis. CONCLUSION: Systemic IL-6 levels are increased, while IL-17A levels are reduced in EAC patients compared to healthy controls. In addition, circulating IL-10 might help to identify patients with advanced disease and high IL-17A might indicate a limited prognosis.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/mortalidade , Interleucina-10/sangue , Interleucina-17/sangue , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/secundário , Feminino , Humanos , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estatísticas não Paramétricas
14.
Cancer Res ; 80(11): 2114-2124, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32269045

RESUMO

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary. SIGNIFICANCE: Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.


Assuntos
Adenocarcinoma/genética , Antígenos CD/genética , Caderinas/genética , Hispano-Americanos/genética , Neoplasias Gástricas/genética , Adenocarcinoma/sangue , Adenocarcinoma/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Células CHO , Cricetulus , Metilação de DNA , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Regiões Promotoras Genéticas , Neoplasias Gástricas/sangue , Neoplasias Gástricas/etnologia , Sequenciamento Completo do Exoma , Adulto Jovem
15.
PLoS One ; 15(4): e0231116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251457

RESUMO

BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS: Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD). RESULTS: Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION: Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.


Assuntos
Adenocarcinoma/diagnóstico , MicroRNA Circulante/genética , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Isoformas de RNA/genética , Adenocarcinoma/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Confiabilidade dos Dados , Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Sensibilidade e Especificidade
16.
Anticancer Res ; 40(4): 2319-2322, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234932

RESUMO

AIM: We investigated blood parameters in patients with inoperable stage III non-small cell lung cancer (NSCLC) to predict individual outcomes after definitive chemoradiotherapy (CRT). PATIENTS AND METHODS: Blood parameters of consecutive patients undergoing definitive CRT between 2010 and 2016 for inoperable stage III NSCLC before multimodal treatment and at first follow-up were measured and analyzed. RESULTS: Blood parameters from 99 patients were evaluated. Histologically, about 50% of patients had an adenocarcinoma. All patients received platinum-based sequential or concurrent CRT. The median total dose to the primary tumor was 60 (range=48-70) Gy. On multivariate analysis after adjustment for all co-founders, median overall survival for pre-treatment cutoffs were: lactate dehydrogenase (LDH) >250 U/l was 17 vs. 27 months [hazard ratio (HR)=2.05, 95% confidence intervaI (CI)=1.15-3.66; p=0.015], thrombocytosis >400×106/l: 11 vs. 23 months (HR=2.75, 95% CI=1.1-6.88; p=0.03), hypoalbuminemia <3.5 g/dl: 12 vs. 24 months (HR=2.42, 95% CI=1.21-4.84; p=0.013) and post-treatment neutrophilia >7×106/l: 12 vs. 27 months (HR=2.5, 95% CI=1.21-5.17; p=0.013). CONCLUSION: Pre-treatment elevated LDH, thrombocytosis, hypoalbuminemia and post-treatment neutrophilia were associated with significantly worse overall survival in patients with inoperable stage III NSCLC treated with CRT. Patients with both pre-therapeutic elevated LDH and hypoalbuminemia demonstrated a dismal prognosis despite completion of multimodal treatment.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Dosagem Radioterapêutica , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Feminino , Humanos , Hipoalbuminemia/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Trombocitose/sangue
18.
Cancer Chemother Pharmacol ; 85(4): 641-650, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32157412

RESUMO

BACKGROUND: Defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma (PDAC) receiving primary chemotherapy is an unmet need. The role of time to CA19-9 nadir and of nadir magnitude was explored in this study. PATIENTS AND METHODS: The databases of our institution's prospective trials were queried to speculate on the time to maximum chemotherapy response. Patients with pathologically proven, metastatic (N = 356) or non-metastatic non-resected (N = 163) PDAC and elevated baseline (> 34 UI/mL) CA19-9 were analyzed. Survival curves were estimated using the Kaplan-Meier method and compared by means of the log-rank test for analyses including at least 45 patients. Multivariable Cox proportional hazards model was used to estimate clinical features for their association with OS. All probability values were from two-sided tests. RESULTS: Time to CA19-9 nadir was ≥ 4 months in 184 of 346 (53%) metastatic and 121 of 163 (74%) non-metastatic patients (p = 0.002). The likelihood of a later nadir was higher with taxane-based chemotherapy as compared to taxane-free combinations (73% versus 56%; p = 0.02). Both metastatic and non-metastatic patients had significantly longer survival when nadir occurred later. Patients with a larger CA19-9 nadir magnitude had significantly longer survival. Metastatic patients with CA19-9 reduced by < 50%, 50-89%, or > 89% and had a median survival of 7.4, 9.8, and 14.7 months, respectively (p ≤ 0.001 for all comparisons). The corresponding figures for non-metastatic patients were 10.6; 17.0; and 18.7 months, respectively (p ≤ 0.02 for < 50% versus 50-89% or > 89%; p = 0.14 for 50-89% versus > 89%). Multivariable analyses showed that time to CA19-9 nadir but not CA19-9 nadir magnitude was independently predictive of survival. CONCLUSION: The present study suggests that a 4-6 months program might be a more suitable candidate for prospective assessment in comparison to shorter pre-defined period in patients who are candidates to surgery after primary chemotherapy.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/mortalidade , Duração da Terapia , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/secundário , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nomogramas , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
19.
In Vivo ; 34(2): 709-714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111774

RESUMO

BACKGROUND/AIM: Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor prognosis for radioactive iodine ablation refractory differentiated thyroid cancer (RR-DTC). Little is known whether NLR can be a tumor marker for RR-DTC patients treated with lenvatinib. PATIENTS AND METHODS: We retrospectively analyzed RR-DTC patients treated with lenvatinib. NLR was calculated at 4 points before and during lenvatinib treatment. RESULTS: The median NLR value increased at the start of lenvatinib treatment, compared to 6 months prior to initiation of lenvatinib treatment. The median overall survival was significantly longer in patients with the lower NLR (<3) at the start of lenvatinib treatment. The median NLR values decreased when the patients achieved best tumor response, and increased again upon disease progression. CONCLUSION: NLR values vary before and during lenvatinib treatment, suggesting that this ratio can reflect disease activity of RR-DTC. NLR can supportively be used as a tumor marker of RR-DTC and an indicator for starting lenvatinib treatment.


Assuntos
Adenocarcinoma/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
20.
Hum Pathol ; 99: 62-74, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171650

RESUMO

Implementation of Grade Groups (GrGrs) has been widely accepted for reporting prostate cancer grade since the 2014 International Society of Urological Pathology consensus meeting. Despite their undisputed value for risk stratification, some GrGr are, a priori, quite heterogeneous in that they contain multiple Gleason patterns (GPs). In this regard, the prognostic significance of GP5 in biopsies with highest GrGr4 is uncertain and evaluated in this study. A search of all core biopsies positive for prostate cancer reviewed after 2005 was performed, and 71 cases with highest GrGr4 containing GP5 (i.e., 3 + 5 = 8 or 5 + 3 = 8; referred to as GrGr4/GP5pos) eligible for inclusion were identified. In addition, 95 core biopsy cases with highest GrGr4 and no GP5 (i.e, 4 + 4 = 8; referred to as GrGr4/GP5neg) were selected for comparison. Multiple pathologic parameters, including volume and amount of GP4, and clinical variables were collected to evaluate the influence of GP5 on disease recurrence, development of metastases, and disease-specific death. GrGr4/GP5pos cases did not show, as a group, statistically significant differences in prostatectomy findings, disease recurrence, metastases, and disease-specific mortality when compared with GrGr4/GP5neg cases. In addition, the risk of all outcomes evaluated in the study did not differ between the whole GrGr4/GP5pos and GrGr4/GP5neg groups. However, Kaplan-Meier analysis found that GrGr4/GP5pos cases with a significant amount of GP4 did show a higher risk of prostate cancer-specific death as well as bone and visceral metastases. Univariate Cox regression demonstrated that preoperative prostate specific antigen (PSA), total number of positive cores, and global GrGr5 were also associated with a higher chance of disease-specific death. In a multivariate model, only global GrGr5 and PSA >20 ng/dL remained statistically significant. This study suggests that the mere presence of GP5 in core biopsies with highest GrGr4 disease may not portend a worse prognosis. In these cases, accounting for the case-wide volume of GP4 by reporting a global GrGr appears to be more relevant as it identifies a subset of GrGr4/GP5pos patients with global GrGr5 who have a higher risk of metastases and prostate cancer-specific mortality.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Gradação de Tumores , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Progressão da Doença , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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