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1.
EClinicalMedicine ; 57: 101834, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36825238

RESUMO

Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88-0.92 in the internal verification and 0.83-0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

2.
Artigo em Inglês | MEDLINE | ID: mdl-36082181

RESUMO

Background: Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis. So far, other than the HER2, GC lacks effective therapeutic targets. Transferrin receptor 1 (TFR1) expressions are abnormally upregulated in various cancers for the satisfaction of iron demand increased. This study aimed to explore the expression and clinical value of TFR1 in GC. Methods: A tissue microarray including GC tissues and matched noncancerous tissues from 155 GC patients were collected. Moreover, the level of TFR1 expression was detected by immunohistochemistry, and we also evaluated the relationship between TFR1 expression and the clinicopathologic characteristics. What is more, univariate analysis and multivariate analysis were used to evaluate the risk factors and independent risk factors affecting the prognosis of GC. Results: We found that TFR1 was overexpressed in GC tissues compared with noncancerous tissues, and a significant relationship was found between TFR1 expression and age (P=0.001), Lauren type (P=0.008), T stage (P=0.003), HER2 (P=0.003), PD-L1 (P < 0.001), and the level of CA72-4 (P=0.028). Survival analysis confirmed that GC patients with positive TFR1 expression had a poorer OS than that with negative TFR1 expression, and TFR1 expression was an independent risk factor in GC. Furthermore, we also found that there was a significant difference between the TFR1-PD-L1- group and the TFR1+PD-L1+ group (P=0.023), while there was no significant difference between the TFR1-PD-L1- group and the TFR1+PD-L1- group (P=0.119), or between the TFR1-PD-L1- group and the TFR1-PD-L1+ group (P=0.396). Conclusions: TFR1 was overexpressed in GC and its aberrant expression identifies a novel potential prognostic marker and therapeutic target. In addition, TFR1 expression may be associated with the immune microenvironment and suppress the immune response via regulating the PD-L1 expression.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35911136

RESUMO

Objective: The aim of this study was to analyze the association between the expression of chromatin assembly factor 1 subunit A (CHAF1A) in gastric cancer (GC) and clinicopathological features, disease prognosis, and expression of programmed cell death-ligand 1 (PD-L1). Material and Methods. A total of 140 GC tissue specimens were collected between January 2013 and December 2017. CHAF1A expression in GC and paracancerous tissues was determined. Then, the associations between CHAF1A expression level in the collected tissues and clinicopathological features as well as PD-L1 expression level were investigated. Cox regression analyses were carried out to determine whether CHAF1A is an independent prognostic factor for GC. Finally, the association between CHAF1A expression levels and survival of the GC patients was investigated. Results: A significantly higher level of CHAF1A expression in GC tissues was found compared to that in paracancerous tissues (p=0.042). CHAF1A expression level in GC tissues was found to be strongly associated with family history (p=0.005), smoking history (p=0.016), T stage (p=0.001), tumor marker AFP (p=0.017), tumor marker CEA (p=0.027), and PD-L1 expression (p=0.029). CHAF1A expression was also found to be positively correlated to PD-L1 expression (p=0.012). Moreover, high CHAF1A expression levels were found to lead to poor prognosis (p=0.019). Univariate and multivariate analyses all showed that CHAF1A was an independent poorer prognostic factor for gastric cancer (p=0.021, HR = 1.175, 95% CI: 1.090-2.890 for univariate analyses; p=0.014, HR = 2.191, 95% CI:1.170-4.105 for multivariate analyses). A high level of CHAF1A expression was thus found to be an independent risk factor for GC prognosis. Conclusion: High CHAF1A expression is associated with poor GC prognosis and positively correlated to PD-L1 expression. Thus, CHAF1A expression level may be used as a novel biomarker for GC diagnosis.

4.
Front Pharmacol ; 13: 911663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35656301

RESUMO

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-ß and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

5.
J Oncol ; 2022: 6065516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756080

RESUMO

Gastric cancer (GC) is a common malignant tumor worldwide and poses a serious threat to human health. As a traditional Chinese medicine, Huaier (Trametes robiniophila Murr.) has been used in the clinical treatment of GC. However, the mechanism underlying the anticancer effect of Huaier remains poorly understood. In this study, we used in vivo imaging technology to determine the anticancer effect of the Huaier n-butanol extract (HBE) on orthotopic and hepatic metastasis of GC mouse models. We found that HBE suppressed tumor growth and metastasis without causing apparent host toxicity. Proteomic analysis of GC cells before and after HBE intervention revealed syntenin to be one of the most significantly downregulated proteins after HBE intervention. We further demonstrated that HBE suppressed the growth and metastasis of GC by reducing the expression of syntenin and the phosphorylation of STAT3 at Y705 and reversing the epithelial-mesenchymal transition (EMT). In addition, we confirmed that syntenin was highly expressed in GC tissue and correlated with metastasis and poor prognosis. In conclusion, our results suggest that Huaier, a clinically used anticancer drug, may inhibit the growth and liver metastasis of GC by inhibiting the syntenin/STAT3 signaling pathway and reversing EMT.

6.
Food Chem ; 368: 130736, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34399179

RESUMO

To systematically identify and quantify the γ- and δ-lactones in Cheddar cheeses, 20 samples from three sources (Ireland, the UK and the USA) were analysed by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), aroma extract dilution analysis, aroma recombination analysis, and aroma addition/omission analysis. Nine lactones were detected in these samples, and one of these lactones, γ-undecalactone, was identified in Cheddar cheese for the first time. The quantitative results showed that the concentration of lactones in these cheeses usually increased as the length of their maturity period increased. γ-Octalactone, γ-undecalactone, γ-dodecalactone, δ-octalactone, δ-decalactone and δ-dodecalactone were identified as aroma-active substances based on their odour activity values and aroma extract dilution analysis, with flavour dilution factors ranging from 2 to 128. Aroma recombination and omission experiments based on a newly developed deodorised Cheddar matrix further validated the important contributions of these lactones to the overall aroma of Cheddar cheeses. The addition of each lactone to aroma recombination models reduced the aroma intensity of sour and rancid properties to various extents and improved the acceptability of the overall flavour.


Assuntos
Queijo , Compostos Orgânicos Voláteis , Queijo/análise , Cromatografia Gasosa-Espectrometria de Massas , Lactonas , Odorantes/análise , Olfatometria , Extratos Vegetais , Compostos Orgânicos Voláteis/análise
7.
Pharmacol Res ; 165: 105411, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401002

RESUMO

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.


Assuntos
Adenocarcinoma/diagnóstico , Antineoplásicos/uso terapêutico , Misturas Complexas/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/metabolismo , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos , Trametes , Resultado do Tratamento
8.
Magn Reson Med ; 85(4): 2145-2159, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33174639

RESUMO

PURPOSE: Intraoperative T2 -weighted (T2-w) imaging unreliably captures image contrast specific to thermal ablation after transcranial MR-guided focused ultrasound surgery, impeding dynamic imaging feedback. Using a porcine thalamotomy model, we test the unproven hypothesis that intraoperative DWI can improve dynamic feedback by detecting lesioning within 30 minutes of transcranial MR-guided focused ultrasound surgery. METHODS: Twenty-five thermal lesions were formed in six porcine models using a clinical transcranial MR-guided focused ultrasound surgery system. A novel diffusion-weighted pulse sequence monitored the formation of T2-w and diffusion-weighted lesion contrast after ablation. Using postoperative T2-w contrast to indicate lesioning, apparent intraoperative image contrasts and diffusion coefficients at each lesion site were computed as a function of time after ablation, observed peak temperature, and observed thermal dose. Lesion sizes segmented from imaging and thermometry were compared. Image reviewers estimated the time to emergence of lesion contrast. Intraoperative image contrasts were analyzed using receiver operator curves. RESULTS: On average, the apparent diffusion coefficient at lesioned sites decreased within 5 minutes after ablation relative to control sites. In-plane lesion areas on intraoperative DWI varied from postoperative T2-w MRI and MR thermometry by 9.6±9.7 mm2 and -4.0±7.1 mm2 , respectively. The 0.25, 0.5, and 0.75 quantiles of the earliest times of observed T2-w and diffusion-weighted lesion contrast were 10.7, 21.0, and 27.8 minutes and 3.7, 8.6, and 11.8 minutes, respectively. The T2-w and diffusion-weighted contrasts and apparent diffusion coefficient values produced areas under the receiver operator curve of 0.66, 0.80, and 0.74, respectively. CONCLUSION: Intraoperative DWI can detect MR-guided focused ultrasound surgery lesion formation in the brain within several minutes after treatment.


Assuntos
Hipertermia Induzida , Cirurgia Assistida por Computador , Animais , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética , Suínos , Tálamo
9.
Anal Chim Acta ; 1095: 197-203, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31864622

RESUMO

Black phosphorus (BP) has a high charge-carrier mobility (∼1000 cm2 V-1 s-1), but the bare BP degrades rapidly in the presence of oxygen and water which limits the application of the BP. In this study, a simple, non-covalent passivation strategy is developed by modifying of the BP with hexamethylendiamine (HA). The functionalized BP exhibits good stability over 4 weeks. The organic phase interdigital electrode which is constructed by stable HA/BP and tyrosinase displays lowest noise signal (0.025 nA) and relatively low detection limit (10 nmol L-1) for bisphenol A. This work provides a new strategy for construction of novel biofuel cell, bioelectronics and biosensors.


Assuntos
Compostos Benzidrílicos/análise , Técnicas Biossensoriais/métodos , Disruptores Endócrinos/análise , Monofenol Mono-Oxigenase/química , Fenóis/análise , Fósforo/química , Compostos Benzidrílicos/química , Benzoquinonas/química , Diaminas/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Disruptores Endócrinos/química , Enzimas Imobilizadas/química , Limite de Detecção , Fenóis/química , Reprodutibilidade dos Testes
10.
Integr Cancer Ther ; 17(2): 477-485, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29108428

RESUMO

BACKGROUND: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. OBJECTIVE: This study aimed to investigate the effect of combining TACE with Kang'ai (KA) injection for treating patients with intermediate stage HCC. METHODS: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). RESULTS: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. CONCLUSION: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Plantas Medicinais/química , Quimioembolização Terapêutica/métodos , Terapia Combinada/métodos , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Medicina Tradicional do Leste Asiático/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(7): 803-808, 2017 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-28722095

RESUMO

OBJECTIVES: To study the correlation between MRI apparent diffusion coefficient (ADC) and expression of Ki-67 in gastric cancers, and to investigate the application of ADC value in diagnosing the malignance of gastric cancer. METHODS: A retrospective cohort analysis was performed on 87 gastric cancer patients who received MRI examination and radical resection at Zhejiang Provincial Hospital of Traditional Chinese Medicine from November 2014 to August 2015. All the postoperative resected samples were confirmed as gastric cancer. Preoperative MRI examination was performed by using Siemens 3.0-T Verio MRI with following parameters: section thickness 3 mm, gap 1 mm, matrix 182×320, field of view 40 cm. Plain scan was followed by T1-weighted fat suppression technique VIBE 3D(TR3.92/TE1.39,90degree) scans at arterial phase (the 30th second), portal venous phase (the 60th second), lag period (the 90th second), axial planes and coronal planes (the 180th second), and sagittal planes (the 210th second), respectively. ADC value of tumor was measured at b-factor of 800 s/mm2 and ADC map was generated from DWI data on the work station. The expression of Ki-67 in cancer tissue was detected by routine immunohistochemical (SP) staining after surgery. Correlation between ADC value and the expression of Ki-67 in gastric cancer was analyzed. RESULTS: Irregular thickening of the gastric wall and inhomogeneous enhancement of the tumor after injection of the contrast material appeared in gastric cancer. Gastric cancer tissue presented hyperintensity and normal gastric wall presented isointensity in DWI image (b=800 s/mm2). Compared with normal gastric tissue, mean ADC value of gastric cancer tissue was significant lower [(1.114±0.265)×10-3 mm2/s vs. (2.032±0.202)×10-3 mm2/s, t=26.209, P=0.000]. The ADC values of high-middle differentiation group, middle-low differentiation group, low differentiation group and signet ring cell carcinoma/mucinous adenocarcinoma group were (1.347±0.234)×10-3 mm2/s, (1.179±0.257)×10-3 mm2/s, (0.996±0.185)×10-3 mm2/s and (1.082±0.230)×10-3 mm2/s, respectively. The difference of mean ADC value among different tumor stages was significant(F=8.498, P=0.000). Along with the Ki-67 expression up-regulated, the ADC value decreased in cancer tissue. The Ki-67 expressions in cancer tissue was negatively correlated with cancer ADC values (r=-0.570, P=0.000). Furthermore, negative correlations of Ki-67 expressions with ADC values of high-middle differentiation group (r=-0.627, P=0.016), low differentiation group (r=-0.787, P=0.000) and signet ring cell carcinoma/mucinous adenocarcinoma group (r=-0.792, P=0.000) were observed respectively, while Ki-67 expression was not correlated with ADC value of middle-low differentiation group. CONCLUSION: The ADC value of gastric cancer can reflect the level of tumor differentiation, and is negatively correlated with Ki-67 expression in cancer tissues.


Assuntos
Imagem de Difusão por Ressonância Magnética , Antígeno Ki-67/metabolismo , Neoplasias Gástricas/diagnóstico por imagem , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo
12.
Diabetes Care ; 38(5): 905-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25710922

RESUMO

OBJECTIVE: The objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking. RESEARCH DESIGN AND METHODS: Study subjects included 859,617 adults with diabetes enrolled for more than 6 months during 2005-2011 in a network of 11 U.S. integrated health care organizations. Inadequate risk factor control was classified as LDL-C ≥100 mg/dL, A1C ≥7% (53 mmol/mol), BP ≥140/90 mm Hg, or smoking. Major CV events were based on primary hospital discharge diagnoses for myocardial infarction (MI) and acute coronary syndrome (ACS), stroke, or heart failure (HF). Five-year incidence rates, rate ratios, and average attributable fractions were estimated using multivariable Poisson regression models. RESULTS: Mean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD. CONCLUSIONS: Additional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Causas de Morte , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/complicações , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Fatores de Risco , Fumar/mortalidade , Acidente Vascular Cerebral/mortalidade , Estados Unidos , Adulto Jovem
13.
J Neurosurg ; 122(1): 152-61, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25380106

RESUMO

OBJECT: In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology. METHODS: Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140-300 W was used for long-duration sonications and 300-700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions. RESULTS: Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages. CONCLUSIONS: This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Ultrassônicos/métodos , Animais , Feminino , Hemorragias Intracranianas/etiologia , Imageamento por Ressonância Magnética , Suínos , Tálamo/cirurgia
14.
Hepatogastroenterology ; 61(132): 1159-64, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26158181

RESUMO

BACKGROUND/AIMS: To investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of late-stage gastric cancer. METHODOLOGY: From July 2008 to February 2011, 72 cases of late-stage gastric cancer that could not be treated with R0 resection were treated prospectively. Patients received 2-4 cycles of paclitaxel plus cisplatin and 5-fluorouracil (PCF regimen) chemotherapy followed by cytoreductive surgery for the primary and metastatic tumors and another 2-4 cycles of PCF chemotherapy post-operatively. The treatment completion rate, patient tolerance and overall survival time were analyzed. RESULTS: There was one perioperative death. The overall response rate (complete and partial response) was 72.2%. Fifty patients (69.4%) completed chemotherapy and surgical resection as planned and 42 (58.3%) cases had R0 resection. The median survival time was 23.5 months (95% CI: 15.8-31.2 months). One-year and 2-year survival rates were 67.0% and 47.0%. The survival time of patients with surgical resection was much longer than that of the non-surgery group (30.2 vs. 8.9 months) (P < 0.01). The survival time of local advanced group was 30.3 months, and was significantly longer than 17.6 months of the distant metastasis group (P < 0.01); however, it had no significant difference compared to 28.2 months of the distant metastasis group with R0 resection. CONCLUSIONS: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for some late-stage gastric cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Gastrectomia , Terapia Neoadjuvante , Neoplasias Gástricas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/mortalidade , Carcinoma/secundário , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Fluoruracila/administração & dosagem , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
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