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1.
ACS Appl Mater Interfaces ; 16(36): 47571-47580, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39223875

RESUMEN

To achieve large-scale hydrogen storage for growing high energy density and long-life demands in end application, the 2LiBH4-MgH2 (LMBH) reactive hydride system attracts huge interest owing to its high hydrogen capacity and thermodynamically favorable reversibility. The sluggish dehydrogenation kinetics and unsatisfactory cycle life, however, remain two challenges. Herein, a bimetallic titanium-niobium oxide with a two-dimensional nanoflake structure (2D TiNb2O7) is selected elaborately as an active precursor that in situ transforms into TiB2 and NbB2 with ultrafine size and good dispersion in the LMBH system as highly efficient catalysts, giving rise to excellent kinetic properties with long-term cycling stability. For the LMBH system added with 5 wt% 2D TiNb2O7, 9.8 wt% H2 can be released within 20 min at 400 °C, after which the system can be fully hydrogenated in less than 5 min at 350 °C and 10 MPa H2. Moreover, a dehydrogenation capacity of 9.4 wt% can be maintained after 50 cycles corresponding to a retention of 96%, being the highest reported to date. The positive roles of TiB2 and NbB2 for kinetics and recyclability are from their catalytic nucleation effects for MgB2, a main dehydrogenation phase of LMBH, thus reducing the apparent activation energy, suppressing the formation of thermostable Li2B12H12 byproducts, and inhibiting the hydride coarsening. This work develops an advanced LMBH system, bringing hope for high-capacity, fast-response, and long-life hydrogen energy storage.

2.
Am J Cancer Res ; 14(8): 3896-3904, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267685

RESUMEN

Therapeutic cancer vaccines are valuable tools for educating the immune system to fight tumors precisely. Cancer cells are characterized with genetic instability and abundant somatic mutations, leading to the production of tumor specific antigens (TSA) called neoantigens. The main goal of neoantigen-based cancer vaccines is to activate the immune system and elicit effective tumor-specific T-cell responses. There have been no reports of advanced esophageal squamous cell carcinoma (ESCC) cases achieving partial remission after personalized mRNA (messenger RNA) vaccine treatment. As personalized neoantigen-based immunotherapies are emerging, here we report a 67-year-old male patient diagnosed with ESCC and multiple enlarged mediastinal lymph nodes, where mRNA vaccines were used for the first time. Tissue samples from the recurrence focus in the esophagus were subjected to whole transcriptome sequencing. The neoantigens were identified by bioinformatics analyses. The top 20 neoantigens were selected to compose the polyneoantigen vaccine, which were administered at 1 mg every 3 weeks for 4 cycles in combination with a PD-1 (programmed death-1) inhibitor. The patient was boosted with a single dose of the PD-1 inhibitor 8 weeks after the 4th cycle. In addition, immune responses were evaluated before and after the 4 cycles of vaccine therapy, and the lesions were evaluated by imaging examination. Our results revealed that neoantigen-based vaccines significantly activated the tumour-specific immune response. TCR (T cell receptor) V-J pairing analysis showed an increase in the abundance of oligoclonal TCRs, indicating improved homogeneity. No grade 3 or higher drug-related adverse events were observed, except for grade 4 thrombocytopenia caused by PD-1 inhibitor treatment. The patient achieved a partial response (PR), with a progression-free survival (PFS) time of 457 days, the OS (overall survival) time of 457 days, and DOR (duration of response) of 377 days. Our report suggests that combining the personalized mRNA vaccine therapy with PD-1 blockade therapy may be an effective treatment strategy for patient with advanced esophageal cancer. However, further clinical trials are necessary to confirm the efficacy and safety of personalized neoantigen-based immunotherapies in the treatment of advanced ESCC. This trial is registered with ClinicalTrials.gov, NCT03468244 on March 16, 2018, and is now complete.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39146704

RESUMEN

Insect guts offer unique habitats for microbial colonization, with gut bacteria potentially offering numerous benefits to their hosts. Although Enterococcus has emerged as one of the predominant gut commensal bacteria in insects, its establishment in various niches within the gut has not been characterized well. In this study, Enterococcus mundtii was inoculated into the silkworm (Bombyx mori L.) to investigate its biological functions. Genome-based analysis revealed that its successful colonization is related to adherence genes (ebpA, ebpC, efaA, srtC, and scm). This bacterium did not alter the activities of related metabolic enzymes or the intestinal barrier function. However, significant changes in the gene expressions levels of Att2, CecA, and Lys suggest potential adaptive mechanisms of host immunity to symbiotic E. mundtii. Moreover, 16S metagenomics analysis revealed a significant increase in the relative abundance of E. mundtii in the intestines of silkworms following inoculation. The intestinal microbiome displayed marked heterogeneity, an elevated gut microbiome health index, a reduced microbial dysbiosis index, and low potential pathogenicity in the treatment group. Additionally, E. mundtii enhanced the breakdown of carbohydrates in host intestines. Overall, E. mundtii serves as a beneficial microbe for insects, promoting intestinal homeostasis by providing competitive advantage. This characteristic helps E. mundtii dominate complex microbial environments and remain prevalent across Lepidoptera, likely fostering long-term symbiosis between the both parties. The present study contributes to clarifying the niche of E. mundtii in the intestine of lepidopteran insects and further reveals its potential roles in their insect hosts.

4.
Bioengineering (Basel) ; 11(4)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38671785

RESUMEN

Powered by biomedical data mining and machine learning technologies, smart healthcare uses cutting-edge medical innovative tools to facilitate the development of sophisticated decision support systems for disease diagnosis and health informatics [...].

5.
Discov Oncol ; 15(1): 124, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639872

RESUMEN

The role of SLC35A2 in breast cancer remains poorly understood, with limited available information on its significance. This study aimed to investigate the expression of SLC35A2 and clinicopathological variables in breast cancer patients. Immunohistochemical analysis of SLC35A2 protein was conductedon 40 adjacent non-neoplastic tissues and 320 breast cancer tissues. The study also assesed the association between SLC35A2 expression and breast cancer clinicopathological features of breast cancer, as well as its impact on overall survival. In comparison to adjacent non-neoplastic tissues, a significantly higher expression of SLC35A2 was observed in breast cancer tissues (P = 0.020), and this expression was found to be independently correlated with HER2 positivity (P = 0.001). Survival analysis indicated that patients with low SLC35A2 expression had a more favorable prognosis in HER2-positive subtype breast cancer (P = 0.017). These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.

6.
Oncol Lett ; 26(4): 418, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37664666

RESUMEN

Malignant ascites (MA) is a common manifestation of advanced gastric cancer (GC) with peritoneal metastasis (PM), which usually indicates a poor prognosis. The present study aimed to explore the effects of MA, a unique microenvironment of PM, on the proliferation of cancer cells and investigate the underlying mechanisms. Ex vivo experiments demonstrated that GC cells treated with MA exhibited enhanced proliferation. RNA sequencing indicated that asparagine synthetase (ASNS) was one of the differentially expressed genes in GC cells following incubation with MAs. Furthermore, the present study suggested that MA induced an upregulation of ASNS expression and the stimulatory effect of MA on cancer cell proliferation was alleviated upon ASNS downregulation. Activating transcription factor 4 (ATF4), a pivotal transcription factor regulating ASNS, was upregulated when cells were treated with MA supernatant. After ATF4 knockdown, the proliferation of MA-treated GC cells and the expression of ASNS decreased. In addition, the decline in the proliferation of the ATF4-downregulated AGS GC cell line was rescued by ASNS upregulation. The findings indicated that MA could promote the proliferation of GC cells via activation of the ATF4-ASNS axis. Hence, it may be a potential target for treating GC with PM and MA.

7.
Am J Transl Res ; 15(1): 316-323, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36777837

RESUMEN

The presence of peritoneal metastasis in patients with pancreatic cancer is associated with poor prognosis. Chemotherapy and radiotherapy may result in poor prognosis in patients with pancreatic cancer. However, immunotherapy improves prognosis even at an advanced stage of the disease. The present study reported a case of a combined therapy of autologous ex vivo expanded natural killer (NK) cells and programmed cell death 1 (PD-1) inhibitor in a patient with pancreatic cancer and peritoneal metastasis. The NK cells were expanded ex vivo and intravenously injected. This was followed by intravenous administration of two dosages of PD-1 inhibitor. Computed tomography and magnetic resonance imaging were performed to assess the size of tumor before and after the combined therapy. In addition, the blood sample and ascites were collected and analyzed before and after the combined therapy. Flow cytometry was carried out to measure the subsets of T cells and macrophages in the collected ascites. Meanwhile, the levels of cytokines in the ascites were quantified through enzyme-linked immunosorbent assay, and Luminex assays were conducted on the supernatant. It was revealed that after the combined therapy, cancer cells disappeared in the ascites, and the T cells were activated, which could be confirmed by the decreased levels of PD-1 and T cell immunoglobulin and mucin domain-containing protein 3. Also, the functioning of macrophages was improved, as shown by the increased level of CD86 and the reduced levels of CD206 and HLA-DR. Notably, the levels of cytokines (transforming growth factor-ß, vascular endothelial growth factor, and interleukin-10) in ascites were significantly upregulated after the combined therapy. In conclusion, it was evident that NK cells combined with PD-1 inhibitor improved the immune microenvironment of carcinomatosis in the peritoneal cavity. Therefore, the combined therapy may be beneficial for suppressing pancreatic cancer and the presence of metastases in the peritoneal cavity. However, there is a need for additional randomized studies to confirm the efficacy of combined therapy.

8.
J Cancer Res Clin Oncol ; 149(7): 3803-3810, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35987927

RESUMEN

OBJECTIVE: To establish an in vitro study model of gastric cancer, gastric cancer organoid culture system, by biopsy under gastroscope, and to explore and analyze the related factors affecting the success rate of culture, to provide a better in vitro model for the study of gastric cancer. METHODS: Twenty-six patients with advanced gastric cancer were collected. Organoids were cultured by biopsy under gastroscope. Paraffin sections were made and HE staining was used to compare the consistency of gastroscopic pathological morphology and organoids. To explore the influencing factors of cultivating gastric cancer organoids in combination with clinical data. RESULTS: A total of 26 cases were collected by gastroscopy, and 12 cases of gastric cancer organoids were successfully cultured after identification, with a success rate of about 48%. Its histopathological morphology was highly consistent with that of gastric cancer. According to the pathological type, 21 cases were poorly differentiated adenocarcinoma and 12 cases were successful. Four cases of signet ring cell carcinoma failed. According to the location of the lesion, the success rate of sampling and culture of gastric antrum was significantly lower, which may be related to antral edema and anatomical characteristics of gastric antrum. Some of the failed cases are related to the quality of sampling, technique and contamination of tissue cells. CONCLUSIONS: We have successfully established gastric cancer organoids through endoscopic biopsy, and analyzed the factors affecting the success rate of culture from various angles, to improve and enhance the organoid culture technology and provide a better platform for tumor research.


Asunto(s)
Adenocarcinoma , Carcinoma de Células en Anillo de Sello , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Adenocarcinoma/patología , Biopsia , Organoides/patología
9.
Gigascience ; 112022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36305606

RESUMEN

BACKGROUND: The motion and interaction of social insects (such as ants) have been studied by many researchers to understand clustering mechanisms. Most studies in the field of ant behavior have focused only on indoor environments (a laboratory setup), while outdoor environments (natural environments) are still underexplored. FINDINGS: In this article, we collect 10 videos of 3 species of ant colonies from different scenes, including 5 indoor and 5 outdoor scenes. We develop an image sequence marking software named VisualMarkData, which enables us to provide annotations of the ants in the videos. (i) It offers comprehensive annotations of states at the individual-target and colony-target levels. (ii) It provides a simple matrix format to represent multiple targets and multiple groups of annotations (along with their IDs and behavior labels). (iii) During the annotation process, we propose a simple and effective visualization that takes the annotation information of the previous frame as a reference, and then a user can simply click on the center point of each target to complete the annotation task. (iv) We develop a user-friendly window-based GUI to minimize labor and maximize annotation quality. In all 5,354 frames, the location information and the identification number of each ant are recorded for a total of 712 ants and 114,112 annotations. Moreover, we provide visual analysis tools to assess and validate the technical quality and reproducibility of our data. CONCLUSIONS: We provide a large-scale ant dataset with the accompanying annotation software. It is hoped that our work will contribute to a deeper exploration of the behavior of ant colonies.


Asunto(s)
Hormigas , Animales , Reproducibilidad de los Resultados , Análisis por Conglomerados , Programas Informáticos
10.
Front Oncol ; 12: 979349, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36158653

RESUMEN

Objective: To examine the clinical values of dual-energy CT parameters derived from dual-layer spectral detector CT (SDCT) in the differential diagnosis of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the gastroesophageal junction (GEJ). Methods: Totally 66 patients with SCC and AC of the GEJ confirmed by pathological analysis were retrospectively enrolled, and underwent dual-phase contrast-enhancement chest CT with SDCT. Plain CT value, CT attenuation enhancement (△CT), iodine concentration (IC), spectral slope (λHU), effective atomic number (Zeff) and 40keV CT value (CT40keV) of the lesion in the arterial phase (AP) and venous phase (VP) were assessed. Multivariate logistic regression analysis was performed to evaluate the diagnostic efficacies of different combinations of dual-energy CT parameters. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of dual-energy CT parameters and Delong test was used to compare AUCs. Results: IC, λHU, Zeff and CT40keV in AP and VP and △CT in VP were significantly higher in the AC group than those in the SCC group (all P<0.05). ROC curve analysis showed that IC, λHU, Zeff and CT40keV in VP had high diagnostic performances, with AUCs of 0.74, 0.74, 0.79 and 0.78, respectively. Logistic regression showed the combination of ICVP, λHU VP, CT40keV VP and Zeff VP had the highest AUC (0.84), with a threshold of 0.40, sensitivity and specificity in distinguishing SCC and AC were 93.1% and 73.0%, respectively. Delong test showed that the AUC of △CTVP was lower than other AUCs of dual-energy CT parameters. Conclusion: Dual-energy CT parameters derived from SDCT provide added value in the differential diagnosis of SCC and AC of the GEJ, especially the combination of IC, λHU, CT40keV and Zeff in VP. Advances in knowledge: Dual-energy CT parameters derived from dual-layer spectral detector CT provide added value to differentiate AC from SCC at the GEJ, especially the combination of effective atomic number, spectral slope, iodine concentration and 40keV CT value in VP.

11.
Sensors (Basel) ; 22(13)2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-35808528

RESUMEN

Humans are able to detect an instantaneous change in correlation, demonstrating an ability to temporally process extremely rapid changes in interaural configurations. This temporal dynamic is correlated with human listeners' ability to store acoustic features in a transient auditory manner. The present study investigated whether the ability of transient auditory storage of acoustic features was affected by the interaural delay, which was assessed by measuring the sensitivity for detecting the instantaneous change in correlation for both wideband and narrowband correlated noise with various interaural delays. Furthermore, whether an instantaneous change in correlation between correlated interaural narrowband or wideband noise was detectable when introducing the longest interaural delay was investigated. Then, an auditory computational description model was applied to explore the relationship between wideband and narrowband simulation noise with various center frequencies in the auditory processes of lower-level transient memory of acoustic features. The computing results indicate that low-frequency information dominated perception and was more distinguishable in length than the high-frequency components, and the longest interaural delay for narrowband noise signals was highly correlated with that for wideband noise signals in the dynamic process of auditory perception.


Asunto(s)
Percepción Auditiva , Ruido , Estimulación Acústica , Acústica , Humanos
12.
Small ; 18(43): e2107013, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35253367

RESUMEN

MgH2 is one of the most promising solid hydrogen storage materials due to its high capacity, excellent reversibility, and low cost. However, its operation temperature needs to be greatly reduced to realize its practical applications, especially in the highly desired fuel cell fields. This work synthesizes a 2D nanoflake-shape bimetallic Ti-Nb oxide of TiNb2 O7 , which has high surface area and shows superior catalytic effect for the hydrogen storage of MgH2 . Incorporated with the TiNb2 O7 nanoflakes as low as 3 wt%, MgH2 shows a low onset dehydrogenation temperature of 178 °C, which is lowered by 100 °C compared with the pristine one. A dehydrogenation capacity as high as 7.0 wt% H2 is achieved upon heating to 300 °C. The capacity retention is as high as 96% after 30 cycles. The mechanism of the improved hydrogen storage properties is analyzed by density functional theory (DFT) calculation and the microstructural evolution during dehydrogenation and hydrogenation. This work provides an MgH2 system with high available capacity and low operation temperature by a unique structural design of the catalyst. The high surface area feature of the TiNb2 O7 nanoflakes and the synthesis method hopefully can develop the application of TiNb2 O7 .

13.
Comput Math Methods Med ; 2022: 6331956, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35222689

RESUMEN

Event-related potentials (ERPs) can reflect the high-level thinking activities of the brain. In ERP analysis, the superposition and averaging method is often used to estimate ERPs. However, the single-trial ERP estimation can provide researchers with more information on cognitive activities. In recent years, more and more researchers try to find an effective method to extract single-trial ERPs, because most of the existing methods have poor generalization ability or suffer from strong assumptions about the characteristics of ERPs, resulting in unsatisfactory results under the condition of a very low signal-to-noise ratio. In this paper, an EEG classification-based method for single-trial ERP detection and estimation was proposed. This study used a linear generated EEG model containing templates of ERP local descriptors which include amplitude and latency, and this model can avoid the invalid assumption about ERPs taken by other methods. The purpose of this method is not to recover the whole ERP waveform but to model the amplitude and latency of ERP components. This method afterwards examined the three machine learning models including logistic regression, neural network, and support vector machine in the EEG signal classification for ERP detection and selected the best performed MLPNN model for detection. To get the utmost out of information produced in the classification process, this study also used extra information to propose a new optimization model, with which outperformed detection results were obtained. Performance of the proposed method is evaluated on simulated N170 and real P50 data sets, and the results show that the model is more effective than the Woody filter and the SingleTrialEM algorithm. These results are also consistent with the conclusion of sensory gating, which demonstrated good generalization ability.


Asunto(s)
Electroencefalografía/clasificación , Electroencefalografía/métodos , Potenciales Evocados/fisiología , Redes Neurales de la Computación , Adulto , Encéfalo/fisiología , Biología Computacional , Simulación por Computador , Electroencefalografía/estadística & datos numéricos , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Modelos Neurológicos , Procesamiento de Señales Asistido por Computador , Relación Señal-Ruido , Máquina de Vectores de Soporte , Adulto Joven
14.
Anticancer Agents Med Chem ; 21(16): 2192-2197, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33397273

RESUMEN

BACKGROUND: Neurokinin-1 receptor antagonists are playing a major advance in Chemotherapy-Induced Nausea and Vomiting (CINV) as powerful prophylactic agents. Therefore, it is significant to find the association between risk factors of patients and CINV so as to adjust the anti-emetic regimens. OBJECTIVE: To evaluate the role of Neurokinin-1 Receptor (NK-1R) antagonist in preventing chemotherapy-induced vomiting in the acute and delayed phases following the first cycle of treatment. METHODS: 145 adult patients with various cancers were recruited in Shanghai Changhai Hospital between September 2017 to November 2017, receiving dual or triple antiemetics. RESULTS: NK-1R antagonist combined with dexamethasone, 5-HT3R antagonist could effectively control delayed- vomiting in patients after Cycle 1 chemotherapy treatment (4.1% vs. 15.6%, P = 0.041<; 0.05). This study also showed that a history of motion sickness was a predictor of chemotherapy-induced vomiting (CINV) (P = 0.023 <; 0.05). In delayed phase a low consumption of alcohol and history of CIV for males were also significantly associated with CINV (P = 0.036 <; 0.05 and P = 0.002 <; 0.05 respectively). CONCLUSION: In this study, we found that triple anti-emetic regimen with NK-1R antagonist could effectively prevent the delayed-vomiting than dual agents. Moreover, some risk factors were observed to be associated with CINV in the delayed phase.


Asunto(s)
Dexametasona/farmacología , Neoplasias/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1/farmacología , Vómitos/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Masculino , Neoplasias/inducido químicamente , Vómitos/inducido químicamente
15.
Oncol Lett ; 20(3): 2757-2762, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32782592

RESUMEN

Gastric cancer (GC) is the third most common cause of cancer-associated mortality in China. Aberrant microRNA (miR) expression can occur through multiple biological processes and has been implicated in cancer development. However, to the best of our knowledge, the function of miR-502-5p in GC is currently unclear. In the present study, the expression and function of miR-502-5p in GC was evaluated. Reverse transcription-quantitative (RT-q) PCR was used to measure the expression levels of miR-502-5p in GC tissues, normal adjacent tissues, a normal human gastric epithelial cell line (GES-1) and two GC cell lines. miR-502-5p expression levels were significantly lower in GC tissues and GC cell lines compared with those in adjacent normal tissues and GES-1 cells, respectively. Subsequently, the target genes of miR-502-5p were predicted, and it was demonstrated that the transcription factor SP1 was a direct target. SP1 expression, cell viability, migration and invasion, and SP1 protein levels were examined using RT-qPCR, an MTT assay, Transwell assay and western blotting, respectively. Human GC cells were then transfected with an miR-502-5p mimic to emulate miR-502-5p overexpression, resulting in inhibition of the proliferation, migration and invasion capacities of human GC cells. Compared with the negative control, cells overexpressing miR-502-5p had decreased levels of SP1 mRNA and protein. These data suggest that miR-502-5p serves as a tumor suppressor gene by targeting SP1 to regulate the proliferation, migration and invasion of GC cells.

16.
J Immunother Cancer ; 8(1)2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32581041

RESUMEN

BACKGROUND: Previous studies have reported that the amplification of some genes, such as Murine Double Minute 2 or 4 and Epidermal Growth Factor Receptor (EGFR), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD. CASE PRESENTATION: A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2-28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues. CONCLUSION: This is the first report on a patient with ESCC harboring rare EGFR kinase domain duplication in exons 2-28 and developing HPD in the process of camrelizumab treatment. This case suggested that EGFR kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring EGFR kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Duplicación de Gen , Neoplasias Hepáticas/secundario , Adulto , Ensayos Clínicos Fase III como Asunto , Progresión de la Enfermedad , Receptores ErbB/genética , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Masculino , Estudios Multicéntricos como Asunto , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Transfus Apher Sci ; 59(5): 102820, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32467007

RESUMEN

BACKGROUND: Because treatment options for coronavirus disease 2019 (COVID-19) are very limited, the use of convalescent plasma has bee explored. CASE PRESENTATION AND TREATMENT: A male centenarian with cough and dyspnea for 2 months was diagnosed with COVID-19. Without effective treatments and with the increased risks of antiviral therapy for the elderly, this patient was given convalescent plasma. The viral load, complete blood count, inflammatory indicators, vital signs, and clinical symptoms were observed before and after COVID-19 convalescent plasma transfusion. RESULTS: After convalescent plasma transfusion, significant improvement was observed on laboratory indicators and clinical symptoms of the patient. Concurrently, SARS-CoV-2 viral load decreased sharply after the first transfusion (from 2.55 × 104 to 1.39 × 103 copies/mL) and became undetectable after the second transfusion. CONCLUSIONS: With the substantial increase of COVID-19 in recent months,treatment for elderly patients has become restricted in some countries. The successful treatment of this 100-year-old patient using convalescent plasma suggests that we should consider adding convalescent plasma in th management of the elderly.


Asunto(s)
COVID-19/terapia , Anciano de 80 o más Años , COVID-19/inmunología , Humanos , Inmunización Pasiva , Masculino , Admisión del Paciente , SARS-CoV-2/fisiología , Resultado del Tratamiento , Sueroterapia para COVID-19
18.
Carcinogenesis ; 41(5): 582-590, 2020 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31740975

RESUMEN

Gastric cancer remains one of the most lethal and prevalent malignancies, particularly in China. The majority of patients are diagnosed with gastric cancer at the late stages of the disease. Besides, the high relapse rate also contributes to the high mortality. Therefore, there exists an imperative need for the development of gastric cancer diagnostic techniques as well as novel indicators for gastric cancer metastasis. Exosomes, secreted by a variety of cell types, play critical roles in intercellular communication, which emerge as promising diagnostic biomarkers for gastric cancer. In this study, we present for the first time, at least to the best of our knowledge, the small RNA sequencing spectra of exosomes derived from the gastric cancer patient plasma using next-generation sequencing, focusing on the exploration of metastasis-related biomarkers. The exosomes enriched from patient plasma samples were well characterized by western blotting, transmission electron microscopy and nanoparticle-tracking analysis. In the following bioinformatic analysis of exosomal miRNAs, three candidates were proposed as the biomarkers for metastasis of gastric cancer, namely miR-10b-5p, miR-101-3p and miR-143-5p, for gastric cancer with lymph node metastasis, gastric cancer with ovarian metastasis and gastric cancer with liver metastasis, respectively. RT-qPCR was performed to test the accuracy of these candidates for validation. In conclusion, we successfully isolated and purified exosomes from plasma of patients with gastric cancer and identified several potential exosomal miRNA markers to distinguish gastric cancer patients with various kinds of metastasis.


Asunto(s)
Biomarcadores de Tumor/genética , Exosomas/genética , Neoplasias Hepáticas/secundario , MicroARNs/genética , Neoplasias Ováricas/secundario , Análisis de Secuencia de ARN/métodos , Neoplasias Gástricas/patología , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Biología Computacional , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Metástasis Linfática , MicroARNs/sangre , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , Pronóstico , Neoplasias Gástricas/sangre , Neoplasias Gástricas/genética , Tasa de Supervivencia , Secuenciación del Exoma
19.
J Cancer Res Clin Oncol ; 145(11): 2637-2647, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31598791

RESUMEN

PURPOSE: Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening. METHODS: Eleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens. RESULTS: Eleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics. CONCLUSIONS: We generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.


Asunto(s)
Antineoplásicos/farmacología , Ascitis/patología , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Técnicas de Cultivo de Órganos/métodos , Organoides/patología , Neoplasias Gástricas/patología , Humanos , Técnicas In Vitro , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Células Tumorales Cultivadas , Secuenciación del Exoma
20.
Int J Oncol ; 54(5): 1591-1600, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30816492

RESUMEN

Drug resistance is a major cause of cancer­associated mortality. Epirubicin­based chemotherapy initially benefits patients with metastatic or advanced gastric cancer; however, tumor recurrence can occur following several courses of treatment. Mitochondrial ribosomal protein L33 (MRPL33)­long (L) and MRPL33­short (S), isoforms of MRPL33 that arise from AS, have been reported to regulate cell growth and apoptosis in cancer; however, few studies have evaluated the roles of MRPL33­L and MRPL33­S in gastric cancer. In the present study, MRPL33­L was demonstrated to be significantly more abundant in gastric tumor tissues than the MRPL33­S isoform. MRPL33­S promoted chemosensitivity to epirubicin in gastric cancer as demonstrated by a chemoresponse assay; chemosensitivity was suppressed in response to MRPL33­L. Gene microarray analysis was performed to investigate the underlying mechanisms. Bioinformatic analysis revealed that overexpression of MRPL33­L and MRPL33­S served critical roles in transcription, signal transduction and apoptosis. In particular, the phosphoinositide 3­kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was markedly regulated. A total of 36 target genes, including PIK3 regulatory subunit α, AKT2, cAMP response element­binding protein (CREB) 1, forkhead box 3, glycogen synthase kinase 3ß and mammalian target of rapamycin, which are involved in the PI3K/AKT signaling pathway, were selected for further investigation via protein­protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, western blot analysis indicated that MRPL33­S promoted the chemoresponse to epirubicin by deactivating PI3K/AKT/CREB signaling and inducing apoptosis, while MRPL33­L had the opposite effects. In conclusion, the results of the present study revealed that isoforms S and L of MRPL33, which arise from alternative splicing, exhibited opposing roles in the chemoresponse to epirubicin in gastric cancer via the PI3K/AKT signaling pathway. These findings may contribute to the development of potential therapeutic strategies for the resensitization of patients with gastric cancer to epirubicin treatment.


Asunto(s)
Empalme Alternativo , Resistencia a Antineoplásicos , Perfilación de la Expresión Génica/métodos , Proteínas Mitocondriales/genética , Proteínas Ribosómicas/genética , Neoplasias Gástricas/genética , Regulación hacia Arriba , Adulto , Anciano , Línea Celular Tumoral , Epirrubicina/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo
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