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1.
Langenbecks Arch Surg ; 409(1): 148, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695994

RESUMEN

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.


Asunto(s)
Anastomosis Quirúrgica , Gastrectomía , Procedimientos de Cirugía Plástica , Neoplasias Gástricas , Humanos , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anastomosis Quirúrgica/métodos , Procedimientos de Cirugía Plástica/métodos , Unión Esofagogástrica/cirugía , Colgajos Quirúrgicos , Yeyuno/cirugía
2.
Pharmacol Res ; 203: 107185, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615875

RESUMEN

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Microbioma Gastrointestinal , Microbiota , Inmunoterapia/métodos
3.
Phytomedicine ; 128: 155535, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537442

RESUMEN

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.


Asunto(s)
Flavonoides , Hipertensión Arterial Pulmonar , Flavonoides/farmacología , Flavonoides/uso terapéutico , Humanos , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Animales , Hipertensión Pulmonar/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Remodelación Vascular/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Medicina Tradicional China/métodos
4.
Front Med (Lausanne) ; 11: 1303855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384412

RESUMEN

Background: SARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection. Methods: The clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported. Results: Female patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto's thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto's thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable "thyrotoxicosis" after infection, suggesting the diagnosis of painless thyroiditis. Conclusion: The five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.

5.
Clin Transl Oncol ; 26(6): 1446-1458, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38190035

RESUMEN

BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.


Asunto(s)
Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Antígeno B7-H1/antagonistas & inhibidores , Adulto , Anciano de 80 o más Años , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Tasa de Supervivencia
6.
Drug Discov Today ; 29(2): 103875, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176674

RESUMEN

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.


Asunto(s)
Antineoplásicos , Productos Biológicos , Neoplasias , Humanos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Medicina Tradicional , Adenosina , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
7.
Heliyon ; 9(8): e19308, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37664726

RESUMEN

Pulmonary fibrosis is an enduring and advancing pulmonary interstitial disease caused by multiple factors that ultimately lead to structural changes in normal lung tissue. Currently, pulmonary fibrosis is a global disease with a high degree of heterogeneity and mortality rate. Nitidine and pirfenidone have been approved for treating pulmonary fibrosis, and the quest for effective therapeutic drugs remains unabated. In recent years, the anti-pulmonary fibrosis properties of natural flavonoids have garnered heightened attention, although further research is needed. In this paper, the resources, structural characteristics, anti-pulmonary fibrosis properties and mechanisms of natural flavonoids were reviewed. We hope to provide potential opportunities for the application of flavonoids in the fight against pulmonary fibrosis.

8.
Angew Chem Int Ed Engl ; 62(40): e202309831, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37594921

RESUMEN

Self-assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis of a new series of carboxylic acid-functionalized porphyrin derivatives, namely AC-1, AC-3, and AC-5, and present, for the first time, a strategy to exploit the large π-moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron-rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double-anchored AC-3 and AC-5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC-5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.

9.
Cancer Res Treat ; 55(3): 1023-1030, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36758956

RESUMEN

PURPOSE: This study aimed to explore the impact of ABL1-tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients' prognosis from TKIs intake practices. Materials and Methods: Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. RESULTS: Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. CONCLUSION: TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Inhibidores de Proteínas Quinasas , Adolescente , Humanos , Niño , Inhibidores de Proteínas Quinasas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Cumplimiento de la Medicación
11.
Front Cell Infect Microbiol ; 12: 969526, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051242

RESUMEN

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Animales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Disbiosis/prevención & control , Medicina de Hierbas , Humanos , Inflamación
12.
Biomed Res Int ; 2022: 7713355, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35224100

RESUMEN

Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3ß, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Codonopsis , Medicamentos Herbarios Chinos/farmacología , Disbiosis/tratamiento farmacológico , Fitoterapia/métodos , Polímero Poliacetilénico/farmacología , Animales , Apoptosis/efectos de los fármacos , Humanos , Masculino , Ratones Desnudos , Raíces de Plantas/química , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Ann Palliat Med ; 10(3): 2971-2978, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33752422

RESUMEN

BACKGROUND: Although the peripherally inserted central catheter (PICC) has been widely utilized, there is still a lack of large sample size-based relevant risk factor investigation for the children with blood diseases in a single center of China. METHODS: We performed a retrospective cohort study through including a total of 2,974 cases aged 0-18 years with blood diseases and PICC insertion. Success rates of different PICC operation techniques were compared. Targeting the common PICC-related complications, we performed the univariate and multivariate logistic regression analyses. Then, based on the screened risk factors, the prediction modeling analysis of binary logistic regression was conducted. RESULTS: The "B-ultrasound plus Seldinger technology" showed a higher success rate of PICC placement than the "non-assistive blind insertion". The catheter type was closely linked to the occurrence of catheter occlusion. The age, insertion site, and catheter type might be the risk factors of phlebitis, while the insertion site, operation season, and catheter type might be associated with catheter fracture. Furthermore, based on these risk factors, we established the nomogram prediction models of phlebitis, rash occurrence, and catheter fracture, respectively, which shows a good predictive ability and a moderate level of predictive accuracy. CONCLUSIONS: Our findings first shed new light on the preoperative estimation of the risk factors of PICCrelated complications for the children with blood diseases in China.


Asunto(s)
Cateterismo Venoso Central , Cateterismo Periférico , Enfermedades Hematológicas , Adolescente , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres , Niño , Preescolar , China , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Factores de Riesgo
14.
Biosci Rep ; 41(2)2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33492335

RESUMEN

Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan-Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4+ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.


Asunto(s)
Mutación , Neoplasias Gástricas/patología , Microambiente Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología
15.
Cancer Manag Res ; 12: 10449-10459, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33122944

RESUMEN

BACKGROUND: Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2), also known as (pro)renin receptor, is implicated in tumorigenesis and the progression of several types of cancer. This study investigated the role of ATP6AP2 in breast cancer. METHODS: UALCAN and ONCOMINE datasets were utilized to compare transcript levels of ATP6AP2 in breast cancer and normal tissues. GOBO datasets were applied to examine ATP6AP2 expression in different breast cancer cell lines. We used the cBioPortal website to explore the gene alterations and copy number alterations of ATP6AP2 in breast cancer. Cell Counting Kit-8 and transwell assays were conducted to evaluate ATP6AP2 function in MCF-7 breast cancer cells. Finally, we used the cBioPortal website to establish the interaction network of ATP6AP2 in breast cancer and performed functional enrichment analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. RESULTS: ATP6AP2 was overexpressed in breast cancer tissues and breast cancer cell lines in the UALCAN, ONCOMINE, and GOBO datasets. The major type of ATP6AP2 alteration was mRNA upregulation. Moreover, ATP6AP2 was most highly expressed in luminal type breast cancer. Finally, ATP6AP2 knockdown reduced MCF-7 cell proliferation, invasion and migration. Functional enrichment analysis suggested that ATP6AP2 regulates several cancer-related pathways, especially the Wnt/ß-catenin signaling pathway. CONCLUSION: Applying multi-dimensional analytical methods, we demonstrate that ATP6AP2 is upregulated in breast cancer and may promote its development and progression.

16.
Exp Ther Med ; 20(2): 1630-1636, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32742395

RESUMEN

Based on its pathological characteristics, breast cancer is a highly heterogeneous disease. Triple negative breast cancer (TNBC) is an aggressive subtype, and due to a lack of effective therapeutic targets, patients with TNBC do not significantly benefit from endocrine or anti-HER2 therapy. Conventional chemotherapy has been regarded as the only systemic therapy option for TNBC, but its therapeutic efficacy remains limited. Estrogen receptor ß (ERß) has been identified as a tumor suppressor in TNBC. Therefore, the aim of the present study was to identify the role of ERß in regulating the response to chemotherapy, and to investigate its underlying mechanism in TNBC. MDA-MB-231 and BT549 cells were treated with doxorubicin (DOX), liquiritigenin [Liq, (Chengdu Biopurify Phytochemicals, Ltd.); a specific ERß agonist], or a combination of DOX and Liq in vitro. The effects of various treatments on cell viability and proliferation were measured using the Cell Counting Kit-8 and colony-formation assays, respectively. MDA-MB-231 and ERß knockdown (ERß-KD) MDA-MB-231 cells were selected for the establishment of ERα-/ERß+ and ERα-/ERß- cell models, respectively. The two cell models were treated with DOX, Liq or a combination of DOX and Liq. The effects of the treatment on the PI3K/AKT/mTOR signaling pathway were evaluated by assessing the protein expression levels of AKT and mTOR using western blot analysis. Low Liq concentrations increased the sensitivity of MDA-MB-231 and BT549 cells to DOX. Moreover, the synergistic effect of Liq and DOX treatment was associated with the inhibition of the PI3K/AKT/mTOR signaling pathway in MDA-MB-231 cells, and the effect was ERß-dependent. The results suggested that elevated ERß expression was associated with sensitivity to doxorubicin by inhibiting the PI3K/AKT/mTOR signaling pathway; therefore, the combined use of conventional chemotherapeutic drugs with ERß agonists may serve as an effective therapy for TNBC.

17.
Medicine (Baltimore) ; 99(14): e19561, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32243373

RESUMEN

Breast cancer is one of the most common malignancies in women worldwide. Many studies have shown that tumor microenvironment cells, immune cells, and stromal cell infiltration have an important impact on prognosis, so it is important to identify biomarkers for achieving better treatment and prognosis.To better understand the relationship between immune and stromal cell-related genes and prognosis, we screened patients with breast cancer in The Cancer Genome Atlas (TCGA) database and divided them into high and low groups based on immune/stromal scores. We next identified differentially expressed immune-related genes that are significantly associated with the prognosis of patients with breast cancer for functional enrichment analysis and protein-protein interaction networks, respectively. Finally, we selected a separate breast cancer cohort in gene expression synthesis (GEO) for validation.Both immune scores and stromal scores are meaningful in the correlation of subtype classification. Disease-free survival of cases with the high score group of immune scores is statistically longer than the cases in the low score group. Differentially expressed immune-related genes extracted from the comparison can effectively evaluate the prognosis of patients with breast cancer and these genes are primarily involved in immune responses, extracellular matrix, and chemokine activity. At last, we obtained a series of verified tumor immune-related genes that predict the prognosis of patients with breast cancer.Combining the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression database and the TCGA database to extract the list of tumor microenvironment related genes which may help to outline the prognosis of patients with breast cancer. Some previously overlooked genes have the potential to become additional biomarkers for breast cancer. Further research on these genes can reveal a new understanding of the potential relationship between tumor microenvironment and breast cancer prognosis.


Asunto(s)
Neoplasias de la Mama/patología , Mediadores de Inflamación/inmunología , Células del Estroma/inmunología , Microambiente Tumoral/fisiología , Factores de Edad , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Bases de Datos Genéticas , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Mapas de Interacción de Proteínas/fisiología
18.
Cell Immunol ; 349: 104063, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32087929

RESUMEN

Extracellular vesicles (EVs), including exosomes, ectosomes and apoptotic vesicles, play an essential role in communication between cells of the innate and adaptive immune systems. Recent studies showed that EVs released after transplantation of allogeneic tissues and organs are involved in the immune recognition and response leading to rejection or tolerance in mice. After skin, pancreatic islet, and solid organ transplantation, donor-derived EVs were shown to initiate direct inflammatory alloresponses by T cells leading to acute rejection. This occurred through presentation of intact allogeneic MHC molecules on recipient antigen presenting cells (MHC cross-dressing) and subsequent activation of T cells via semi-direct allorecognition. On the other hand, some studies have documented the role of EVs in maternal tolerance of fetal alloantigens during pregnancy and immune privilege associated with spontaneous tolerance of liver allografts in laboratory rodents. The precise nature of the EVs, which are involved in rejection or tolerance, and the cells which produce them, is still unclear. Nevertheless, several reports showed that EVs released in the blood and urine by allografts can be used as biomarkers of rejection. This article reviews current knowledge on the contribution of EVs in allorecognition by T cells and discusses some mechanisms underlying their influence on T cell alloimmunity in allograft rejection or tolerance.


Asunto(s)
Aloinjertos/inmunología , Vesículas Extracelulares/inmunología , Rechazo de Injerto/inmunología , Tolerancia al Trasplante/inmunología , Inmunidad Adaptativa , Animales , Presentación de Antígeno , Células Presentadoras de Antígenos/inmunología , Biomarcadores , Quimerismo , Vesículas Extracelulares/metabolismo , Femenino , Xenoinjertos/inmunología , Humanos , Inmunidad Innata , Isoantígenos/inmunología , Masculino , Intercambio Materno-Fetal/inmunología , Ratones , Embarazo
19.
J Cell Biochem ; 121(8-9): 3854-3860, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31709598

RESUMEN

This study aimed to identify prognostic long noncoding RNAs (lncRNAs) signature for predicting the prognosis of patients with rectal cancer. LncRNA-sequencing data and clinicopathological data of patients with rectal cancer were retrieved from The Cancer Genome Atlas database. Univariate and multivariate Cox proportional hazards regression analysis, the least absolute shrinkage, and selection operator analysis and the Kaplan-Meier curve method were employed to identify prognostic lncRNAs and construct multi-lncRNA signature. Finally, five lncRNAs (AC079789.1, AC106900.2, AL121987.1, AP004609.1, and LINC02163) were identified to construct a five-lncRNA signature. According to the five-lncRNA signature, patients with rectal cancer were divided into a high-risk group and low-risk group. Patients with rectal cancer had significantly poorer overall survival in the high-risk group than in the low-risk group. We used a time-dependent receiver operating characteristic curve to assess the power of the five-lncRNA signature by calculating the area under the curve (AUC). The AUCs for predicting 3-year survival and 5-year survival were 0.742 and 0.935, respectively, which indicated a good performance of the five-lncRNA signature. The five-lncRNA signature was independently associated with the prognosis of patients with rectal cancer through using univariate and multivariate Cox regression analysis. The biological function of the five lncRNAs was enriched in some cancer-related biological processes and pathways by performing functional enrichment analysis of their correlated protein-coding genes. In conclusion, we developed a five-lncRNA signature as a potential indicator for rectal cancer.

20.
J Eval Clin Pract ; 26(1): 290-298, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31115960

RESUMEN

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are widely performed to cure obesity and obesity-related diseases. Our aim was to compare these two procedures. MATERIALS AND METHODS: An electronic literature search was performed from inception to December 2018. The clinical outcomes between LSG and LRYGB were pooled using software RevMan5.3. RESULTS: A total of 1076 patients from 11 studies were analysed. LSG had shorter operation time (mean difference [MD] = -33.81; 95% confidence interval [CI], -46.04 to -21.57; P < .00001) and less early complications rate (risk ratio [RR] = 0.55; 95% CI, 0.36-0.84; P = .005) compared with LRYGB. There were no significant difference about the readmission rate (RR = 0.57; 95% CI, 0.21-1.54; P = .27) and re-operation rate (RR = 0.43; 95% CI, 0.14-1.27; P = .13) between LSG and LRYGB. The conversion to open rate and mortality rate within 30 days was low in both LSG and LRYGB. Mean hospital stay in LSG group (0.3-5.2 d) seems shorter than that in the LRYGB group (2.3-6.6 d). As to the effect of LSG and LRYGB on the percentage of excess weight loss (EWL), there was no significant difference between these two surgeries in EWL (MD = -4.05; 95% CI, -8.89 to 0.80; P = .10). LSG was equal to LRYGB on remission of T2DM (RR = 0.94; 95% CI, 0.84-1.06; P = .31). CONCLUSIONS: Both LSG and LRYGB can be performed with very low conversion to open rate and mortality rate. The readmission rate and re-operation rate are comparable between these two surgeries. The efficacy of these two surgeries on EWL and T2DM is equivalent, but LSG has an advantage over LRYGB in operation time and early complications rate.


Asunto(s)
Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Gastrectomía , Humanos , Obesidad Mórbida/cirugía , Resultado del Tratamiento
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