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1.
PLoS One ; 14(9): e0222024, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483849

RESUMO

The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.

2.
Ann Surg Oncol ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376034

RESUMO

BACKGROUND: A multicenter phase 2 trial analysed chemoselection with docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for locally advanced unresectable esophageal cancer. This study presents updated 3-year analyses to further characterize the impact of DCF-ICT followed by CS. METHODS: Esophageal cancer patients with clinical T4 disease, unresectable supraclavicular lymph node metastasis, or both were eligible for this study. The treatment starts with DCF-ICT, followed by CS if the cancer is resectable, or by concurrent chemoradiation if it is not resectable. This updated analysis presents 3-year overall survival (OS), 3-year progression-free survival (PFS), and pattern of relapse. RESULTS: The median follow-up period for the patients surviving without death was 39.3 months. The estimated 1-year OS was 66.7%, and the lower limit of the 80% confidence interval (CI) was 54.6%. The estimated 3-year OS was 46.6% (95% CI 34.2-63.5%). The OS for the patients who underwent R0 resection (n = 19) was significantly longer than for those who did not (3-year OS: 71.4% vs. 30.1%). The estimated 1-year PFS was 50.6%, and the 3-year PFS was 39.6%. The PFS for R0 was significantly longer than for non-R0 (3-year PFS: 61.3% vs 25.0%). Recurrence or progression at the primary site was observed in 31% of the non-R0 group. The rate of distant metastasis did not differ significantly between the non-R0 and R0 groups (21% vs 16%). CONCLUSIONS: Long-term follow-up evaluation confirmed that DCF chemoselection aimed at CS is feasible and promising in terms of survival for patients with locally advanced esophageal cancer.

3.
Jpn J Clin Oncol ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411696

RESUMO

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.

5.
Dig Endosc ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31295769

RESUMO

OBJECTIVES: Neoadjuvant chemotherapy (nCT) followed by surgery is one of the standard treatments for resectable esophageal squamous cell carcinoma (ESCC). According to the Response Evaluation Criteria in Solid Tumors, endoscopic evaluation of a primary lesion is not recommended during nCT because of reduced objectivity. This study aimed to develop and validate endoscopic evaluation criteria for nCT. METHODS: This study retrospectively investigated patients with T2/3 ESCC who underwent nCT followed by radical esophagectomy across two institutions (test and validation sets). We retrospectively estimated the therapeutic effect by classifying patients according to degree of tumor shrinkage (evaluated with endoscopy) as follows: marked reduction (MR), half reduction (HR), insufficient reduction (IR), and progressive disease (PD). Three endoscopists evaluated patients in the test set. Another three endoscopists evaluated patients in the validation set. We analyzed recurrence-free survival (RFS) 3 years after surgery. RESULTS: Of 129 patients in the test set, 44 had MR, 35 had HR, 44 had IR, and six had PD. The 3-year RFS rates were 55% (overall), 79% (MR), 54% (HR), 35% (IR), and 33% (PD). Of 91 patients in the validation set, 22 had MR, 49 had HR, 18 had IR, and two had PD. The 3-year RFS rates were 54% (overall), 77% (MR), 55% (HR), 22% (IR), and 50% (PD). CONCLUSIONS: Our endoscopic criteria for nCT predicted prognosis; however, future studies are needed to further investigate our criteria before general application in the clinical setting.

6.
Circ Arrhythm Electrophysiol ; 12(8): e007311, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31345092

RESUMO

BACKGROUND: Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM. METHODS: A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10-30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up. RESULTS: The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (P=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (P=0.077). CONCLUSIONS: USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021127.

7.
In Vivo ; 33(4): 1363-1368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280231

RESUMO

BACKGROUND/AIM: When possible, surgical resection is recommended for local recurrence after resection of colorectal cancer. In unresectable cases, chemotherapy is usually indicated, although the success of chemoradiotherapy (CRT) in this setting is unclear. PATIENTS AND METHODS: We retrospectively reviewed the treatment outcomes of 18 patients who received CRT for unresectable local recurrence after radical colorectal cancer surgery at our hospital between January 2000 and May 2016. RESULTS: Of these 18 patients, three experienced complete response and four experienced partial response, resulting in a 39% overall response. With a median follow-up time of 42 months, the 5-year progression-free survival and overall survival were 34.8% and 54.4%, respectively; associated with a median local failure-free survival time of 40.9 months. Two of the three patients that underwent CRT remained local failure free for 5 years. CONCLUSION: CRT for local recurrence of rectal cancer without distant metastasis produces similar overall survival rates and local control as conventional surgical resection.

8.
J Am Heart Assoc ; 8(15): e010881, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31311438

RESUMO

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

9.
Jpn J Clin Oncol ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287877

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer for which no standard systemic chemotherapy has been established. While cisplatin plus pemetrexed, the standard treatment for malignant pleural mesothelioma (MPlM), is usually used for MPeM, its efficacy remains unclear. METHODS: We retrospectively reviewed the medical charts of MPeM patients who had received cisplatin plus pemetrexed as first-line chemotherapy between January 2001 and July 2016 at the National Cancer Center Hospital. Patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day1, repeated every 3 weeks until progressive disease, unacceptable toxicities or patient's refusal to continue. RESULTS: A total of 29 MPeM patients received cisplatin plus pemetrexed. Median progression-free survival and overall survival were 7.1 months (95% CI: 4.8-9.3) and 15.4 months (95% CI: 9.5-21.2), respectively. Among 16 patients with measurable lesions, the response rate was 38%. Incidences of grade 3/4 leukopenia, neutropenia, anemia and thrombocytopenia were 21%, 17%, 14% and 3%, respectively. Non-hematological toxicities were mild, and there were no treatment-related deaths. CONCLUSIONS: Cisplatin plus pemetrexed, showing consistent efficacy with MPlM, can be recommended as first-line treatment for unresectable MPeM patients.

10.
Anticancer Res ; 39(7): 3931-3936, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262923

RESUMO

BACKGROUND/AIM: Platinum plus 5-fluorouracil (FP) is a first-line regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (RM-ESCC). In this retrospective study, we evaluated the efficacy and safety of S-1 monotherapy as a salvage line treatment for RM-ESCC, focusing on the reasons for discontinuation of prior FP. MATERIALS AND METHODS: The subjects of this study had RM-ESCC and received S-1 after failure of FP. RESULTS: Eleven patients were enrolled. Nine patients were refractory and two were intolerant to prior FP. The median progression-free survival and overall survival time were 3.0 and 11.7 months, respectively. Overall response rate was 22.2% and disease control rate of the 11 patients was 36.4%. Median relative dose intensity of 5-FU was 100% (range=85-100%). CONCLUSION: S-1 efficacy in RM-ESCC when given after FP was modest. Favorable OS may be attributed to good local control rather than to the efficacy of S-1 monotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Cisplatino/uso terapêutico , Combinação de Medicamentos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Terapia de Salvação , Falha de Tratamento
11.
Invest New Drugs ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264067

RESUMO

Background Ramucirumab (RAM) plus solvent-based (sb)-paclitaxel (PTX) is the standard second-line chemotherapy for advanced gastric cancer (AGC). The subset analysis of the ABSOLUTE trial, which confirmed non-inferiority of weekly nanoparticle albumin-bound (nab)-PTX to weekly sb-PTX, suggested that nab-PTX might have better efficacy than sb-PTX in patients with peritoneal metastasis. We retrospectively evaluated the efficacy and safety of RAM plus sb-PTX and nab-PTX in patients with peritoneal metastasis of AGC. Methods AGC patients who received RAM plus sb-PTX or nab-PTX as second-line chemotherapy from June 2015 to February 2019 were included in the study. Overall survival (OS), progression-free survival (PFS), response rate, and safety were assessed. Results A total of 128 patients were included in this study (93 in the RAM plus sb-PTX group and 35 in the RAM plus nab-PTX group). PFS was 4.1 months in the RAM plus sb-PTX group and 4.6 months in the RAM plus nab-PTX group (HR 0.90; 95%CI 0.58-1.41, p = 0.643). OS was 8.9 months in the RAM plus sb-PTX group and 11.4 months in the RAM plus nab-PTX group (HR 0.95; 95%CI 0.56-1.62, p = 0.847). A total of 62 and 31 patients had peritoneal metastasis in the RAM plus sb-PTX and the RAM plus nab-PTX groups, respectively. RAM plus nab-PTX showed a slightly longer survival compared to RAM plus sb-PTX in patients with peritoneal metastasis (PFS 5.8 vs 3.5 months, HR 0.66; 95% CI 0.40-1.10, p = 0.109). Conclusion This study suggests that RAM plus nab-PTX might be a more effective treatment for peritoneal metastasis of AGC.

12.
Esophagus ; 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222680

RESUMO

BACKGROUND: Definitive chemoradiotherapy is one of the treatment options for locally advanced esophageal cancer with curative intent. Esophagitis and pharyngitis are well-known adverse events that occur during chemoradiotherapy, but gastric mucosal injury has been less frequently reported compared to mucositis. Importantly, gastric mucosal injury is not well known, hard to manage, and sometimes fatal. Hence, we examined the clinical characteristics and the incidence of gastric mucosal injury after CRT for esophageal cancer. METHODS: The medical records of patients who received definitive chemoradiotherapy combined with 5-fluorouracil and cisplatin for stage II/III (nonT4) esophageal squamous cell carcinoma from January 2001 to December 2010 at our institute were reviewed retrospectively. RESULTS: We investigated 256 patients in whom, data for endoscopic abdomen examinations were both before and after CRT were available. Gastric mucosal damage was observed in 90 patients (35%) (grade 1/2/3 = 69/18/3). One of the possible risk factors identified in this study was the irradiation dose to abdomen. Compared to patients with cervical esophagus-upper thoracic esophagus tumor location, patients with middle thoracic esophagus-abdominal esophagus tumor location were more likely to develop gastric mucosal damage, although there was no statistically significant difference. CONCLUSIONS: It is important to consider gastric mucosal injury in patients who receive CRT, particularly when the irradiation field includes stomach.

13.
Intern Med ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31243228

RESUMO

Objective We compared the pain accompanying the injection of high-concentration (300 units/mL) insulin glargine (U300G) with that accompanying the injection of conventional (100 units/mL) insulin glargine (U100G). Methods U100G was switched to U300G at basically the same dosage. Visual analog scales were used to assess the quality of life (QOL). The primary outcome was the change in the pain accompanying injections in those using ≥30 units of U100G compared with those using <30 units at baseline. Standardized mean differences (Cohen's d) were used to measure the effect size. Patients Adult patients with type 2 diabetes mellitus using U100G. Results One hundred and eight patients were recruited. The numbers of patients who used U100G at ≥30 units, 20 to <30 units, 10 to <20 units, and <10 units were 13, 14, 34, and 47, respectively. The improvement in the pain score was not significant for ≥30 units compared with <30 units (-50.3±24.0 vs. -40.4±28.5, p=0.25, d=0.38), but a significant difference was observed for ≥20 units compared with <20 units (-50.8±22.7 vs. -38.4±29.1, p=0.03, d=0.48), as well as for ≥10 units compared with <10 units (-48.1±25.0 vs. -33.0±29.7, p<0.01, d=0.56). When all patients were analyzed together, significant improvements in the pain score (-41.5±28.0, p<0.01), ease of use score (-37.5±32.2, p<0.01), force needed to inject score (-46.5±28.6, p<0.01), and preference for U300G compared with U100G score (-45.8±33.1, p<0.01) were observed. Conclusion There is possibility that switching from U100G to U300G might be associated with better QOL for patients who require insulin glargine injections. To prove this hypothesis, a randomized controlled trial (preferably double-blinded) will be required in the future.

14.
Cancer Sci ; 110(8): 2590-2599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169336

RESUMO

Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real-time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial-mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label-free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next-generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first-phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second-phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)-specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time-dependent genetic alterations that appeared during anti-EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095).


Assuntos
DNA Tumoral Circulante/genética , DNA de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Molécula de Adesão da Célula Epitelial/genética , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Mutação/genética
15.
Gastric Cancer ; 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31087200

RESUMO

BACKGROUND: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. METHODS: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. RESULTS: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001). CONCLUSIONS: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

16.
Eur Heart J ; 40(26): 2142-2151, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31098611

RESUMO

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

17.
JAMA Netw Open ; 2(5): e194573, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31125107

RESUMO

Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

18.
Eur Heart J ; 40(26): 2171, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977799
19.
Nat Commun ; 10(1): 1299, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898996

RESUMO

Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/diagnóstico , Ácidos Nucleicos Livres/genética , MicroRNAs/genética , Neoplasias/diagnóstico , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/genética , Neoplasias/patologia , Análise de Componente Principal , Reação em Cadeia da Polimerase em Tempo Real , Sarcoma/sangue , Sarcoma/genética , Sarcoma/patologia , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/sangue , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Transcriptoma
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