RESUMO
AIM: To introduce a novel endo-luminal balloon-assisted drainage (EBAD) and compare postoperative complication rates between EBAD and diverting stoma (DS) groups. METHODS: The single center prospective non-random cohort study included a total of 163 patients in convenience patients with rectal cancer between January 2019 and January 2021. Out of 163 patients, 83 underwent DS and 80 EBAD. Primary endpoints were postoperative complication rate. RESULTS: The total number of complications was 28 in the DS group vs. 22 in the EBAD group (P = 0.388). 18 patients (21.7%) in the DS group and 14 patients (17.5%) in the EBAD group developed postoperative complication (P = 0.501). There were no differences identified for anastomotic leak rates between the two groups (P = 0.677). The rate of the pelvic abscess was lower in the EBAD group (1/80, 1.3%) than in the DS group (4/83, 4.8%) but with no statistical significance (P = 0.386). Compared with the DS group, the median operative time was shorter in the EBAD group (225 vs. 173.5 min, P < 0.001). Regarding incomplete small bowel obstruction, a higher prevalence was observed in the DS group compared to the EBAD group (7.2% vs 2.5%, P = 0.301). 7 patients (11.3%) in the DS group developed a para-stomal hernia, while no patient suffered a catheter-related complication. The median postoperative hospital stay was shorter in the DS groups than in the EBAD group (7 vs 8 days, P = 0.009). The median residence time of endo-luminal balloon-assisted drainage was 5.41 days. The median average and total volume of drainage were 51.57 ml/day and 255 ml, respectively. CONCLUSION: EBAD is feasible and safe with similar postoperative complications when compared with a DS. EBAD may replace DS after rectum resection.
Assuntos
Neoplasias Retais , Reto , Anastomose Cirúrgica , Estudos de Coortes , Drenagem/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: Myeloid-derived suppressors cells (MDSCs) are heterogeneous immunosuppressive cells, closely related to the development, efficacy and prognosis in various tumors. The relationship between clinicopathological characteristics, efficacy of neoadjuvant chemoimmunotherapy (NCIO) and circulating MDSCs in patients with non-small cell lung cancer (NSCLC) was investigated in this study. METHODS: This study analyzed the clinical data of patients diagnosed at Department of Thoracic Surgery, Beijing Chest Hospital from November 2020 to August 2021. MDSCs and T cells subgroups were measured in fresh peripheral blood mononuclear cells(PBMCs) at baseline. Flow cytometry was used to detect MDSCs and T cells subgroups. RESULTS: A total of 78 patients with NSCLC and 20 patients with benign nodule underwent direct surgery. 23 patients with NSCLC scheduled to accept NCIO before surgery. NSCLC had elevated levels of total MDSCs, PMN-MDSCs and M-MDSCs compared to patients with benign nodule. MDSCs subgroups were correlated to the pTNM stage in NSCLC patients. The frequency of total MDSCs were moderately positively correlated with regulatory T cells (Tregs)(r = 0.3597, P < 0.01) and negatively correlated with CD4 + T cells(r = 0.2714, P < 0.05). The baseline levels of total MDSCs, PMN-MDSCs and Tregs in pCR patients were significantly decreased than those of non-pCR patients (P < 0.05). CONCLUSION: Circulating MDSCs were increased in NSCLC patients. MDSC subgroups were related to pTNM stage in NSCLC patients. Total MDSCs were positively correlated with Tregs levels and negatively correlated with CD4 + T cells in peripheral blood. The level of MDSCs and Tregs in peripheral blood may have potential value in predicting pathological response in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Supressoras Mieloides , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Leucócitos Mononucleares/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Células Supressoras Mieloides/patologia , Terapia NeoadjuvanteRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignant tumors of the digestive system. Many patients are diagnosed at an advanced stage and lose eligibility for surgery. Moreover, there are few effective methods for treating pancreatic ductal cell carcinoma. Increasing attention has been given to microRNAs (miRNAs) and their regulatory roles in tumor progression. In this study, we investigated the effects of exosomes extracted from human umbilical cord mesenchymal stem cells (HUCMSCs) carrying hsa-miRNA-128-3p on pancreatic cancer cells. METHODS: Based on existing experimental and database information, we selected Galectin-3, which is associated with pancreatic cancer, and the corresponding upstream hsa-miRNA-128-3p. We extracted HUCMSCs from a fresh umbilical cord, hsa-miRNA-128-3p was transfected into HUCMSCs, and exosomes containing hsa-miRNA-128-3p were extracted and collected. The effect of exosomes rich in hsa-miRNA-128-3p on pancreatic cancer cells was analyzed. RESULTS: The expression of Galectin-3 in normal pancreatic duct epithelial cells was significantly lower than that in PDAC cell lines. We successfully extracted HUCMSCs from the umbilical cord and transfected hsa-miRNA-128-3p into HUCMSCs. Then we demonstrated that HUCMSC-derived exosomes with hsa-miRNA-128-3p could suppress the proliferation, invasion, and migration of PANC-1 cells in vitro by targeting Galectin-3. CONCLUSION: Hsa-miRNA-128-3p could be considered as a potential therapy for pancreatic cancer. We provided a new idea for targeted therapy of PDAC.
Assuntos
Carcinoma Ductal Pancreático/patologia , Exossomos/fisiologia , Galectina 3/fisiologia , Células-Tronco Mesenquimais/ultraestrutura , Neoplasias Pancreáticas/patologia , Cordão Umbilical/citologia , Humanos , Células Tumorais CultivadasRESUMO
Chemotherapy is one of the most commonly used clinical treatments among the currently available cancer therapies. However, the phenomenon of Multidrug resistance (MDR) has become a challenge in the treatment process, weakening the impact of chemotherapy. Extensive research on elucidating the development of cancer MDR has identified the following mechanisms that play a critical role in the development of several MDR reversal agents: abnormal expression of cell membrane transporters, adaptation of cancer cells to the microenvironment, regulation of hypoxia, repair of DNA damage and reduction of apoptosis, the enhancement of the EMT process, the existence of cancer stem cells (CSCs), and the abnormal activation of key signaling pathways. However, they failed to demonstrate significant efficacy due to severe side effects during their clinical trials. Traditional Chinese medicines (TCMs) are known to play an important anti-cancer role since they have low toxicity, high efficacy, and safety and can reverse MDR. TCMs reversal agents can be divided into Chinese medicine monomers, synthetic monomers, analogs, or derivatives. Several studies have shown that TCMs can effectively overcome cancer MDR and can be effectively used for treating cancer patients.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico , HumanosRESUMO
This study was conducted to investigate effects of vitamin A (VA) and vitamin K3 (VK3) on immune function and intestinal antioxidant capacity of aged laying hens. In a 3 × 3 factorial arrangement, the diets of 1080 Roman Pink laying hens (87 weeks old) was formulated with deficient, adequate and excess VA and VK3, including 0, 7000 and 14000 IU/kg VA and 0, 2.0 and 4.0 mg/kg VK3 for 8 weeks. Interactive effects between VA and VK3 were observed that VA and VK3 decreased the splenetic mRNA expression of inducible nitric oxide synthase (iNOS) and tumour necrosis factor α (TNF-α), but increased the plasma immunoglobulin G (IgG) content and jejunal mRNA expression of nuclear factor-like 2 (Nrf2). Hens fed adequate or excess VA had higher spleen index, mRNA expression of interleukin-10 (IL-10) in spleen, sIgA content, catalase (CAT), glutathione peroxidase and total dismutase (T-SOD) activity, and mRNA expression of polymeric immunoglobulin receptor (pIgR) in jejunum and lower mRNA expression of IL-1ß in jejunum and iNOS, TNF-α in spleen. Furthermore, adequate or excess VK3 significantly increased plasma IgG content, the CAT, T-SOD and total antioxidant capacity activities, up-regulated the mRNA expression of pIgR, Nrf2, SOD1 and CAT in jejunum and down-regulated the mRNA expression of iNOS and TNF-α in spleen.(AU)
Assuntos
Vitamina A/efeitos adversos , Galinhas/imunologia , Vitamina K 3/efeitos adversos , Sistema Imunitário , Antioxidantes/análiseRESUMO
Geese (Anser cygnoides) possess stronger ability of roughage digestion and utilization than other poultries, hence, it has become the focus of attention of scientists. Duodenal, jejunum and ileum were mainly participated in food digestion and nutrient absorption, while the cecum was responsible for biological fermentation. Effects on the geese's cecal microbiota community by feeding with the all-grass diet have been investigated, however, whether it had an influence on the geese's duodenal microbiota community remains unexplored. To address this problem, geese feeding with the basal diet for 28 days (G1), the basal diet for 28 days and the all-grass diet for the following 14 days (G2), the basal diet for 42 days (G3) were selected, respectively. The duodenal segments of geese were collected and the hypervariable V3-V4 region of the bacterial 16S rRNA gene was sequencing. A total of 4 main phyla and 16 main genera were identified. Moreover, we also successfully identified that two taxa including the Helcococcus and Clostridium could be used as distinguishing biomarkers specific to G2. The functional profiles of the duodenum microbiota were mainly involved in the membrane transport (e.g. ABC transporters), amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling pathways in geese feeding with the all-grass diet. In conclusion, the all-grass diet could impact the composition of duodenal microbiota. However, to resolve the underlying mechanism of the fiber digesting and utilization in geese's gut microbiota, the whole intestinal system needs to be assessed by further studies.(AU)
Assuntos
Animais , Microbiota , Microbioma Gastrointestinal , Gansos/fisiologia , Ração Animal , Ingestão de Alimentos/fisiologiaRESUMO
Cancer is a serious public health problem in the world and the prevention and control of cancer has become one of the health strategies of governments around the world. According to the data of the International Agency for Research on Cancer (IARC), about 8 million people die of cancer every year in the world. With the continuous progress of medical technology, there are many methods to treat cancer at present. However, many treatment methods have achieved different therapeutic effects, some of them have obvious toxic and side effects. Therefore, it is necessary to study simpler and more effective new therapies for alleviating pain and prolonging lifetime of patients. In this view, we focus on the application progress of CRISPR system in some major cancers and its potential in cancer treatments.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Neoplasias/genética , Neoplasias/terapia , Proteínas de Bactérias , Proteína 9 Associada à CRISPR , Proteínas Associadas a CRISPR , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Endodesoxirribonucleases , Feminino , Técnicas de Inativação de Genes , Terapia Genética , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Linfoma/genética , Linfoma/terapia , Masculino , Mutação , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Pesquisa , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologiaRESUMO
This study aimed to investigate the effect of Lactobacillus plantarum DPP8 and Lactobacillus acidophilus C7282 in feed supplementation on growth performance, Salmonella invasion, inflammation, and mediating signaling in broilers infected with Salmonella Typhimurium (S. Typhimurium). A total of 240 broilers at day old were randomly allocated into four groups, orally infected with S. Typhimurium and supplemented with individual or combined Lactobacilli DPP8 and C7282 at doses of 0 (control), 1010 (individual), or 2.0 × 1010 (combination) cfu/kg of diet for 21 d. The results showed that supplementing Lactobacilli improved (p 0.05) feed intake and body weight gain and decreased (p 0.05) S. Typhimurium load in the caecum, harder gland, spleen and bursa of Fabricius. Also, the supplements decreased (p 0.05) interleukin (1/2/4), tumor necrosis factor and interferon in the serum, enhanced (p 0.05) interleukin 10, and downregulated gene expressions of inflammatory mediators including Janus kinase (Jak2/3), signal transducer and activator of transcription protein (STAT3/4/5/6) in the intestinal mucosa. In contrast, diets containing DPP8 exhibited greater effects on the inhibition of the pathogen and inflammatory response than C7282. The obtained data suggest that Lactobacilli C7282 and DPP8 can be used as feed additives to inhibit colonization and translocation of S. Typhimurium and inflammatory responses via downregulating Jak/STAT signaling in broilers.(AU)
Assuntos
Animais , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Lactobacillus/química , Intoxicação Alimentar por Salmonella , Salmonella typhimuriumRESUMO
This study aimed to investigate the effect of Lactobacillus plantarum DPP8 and Lactobacillus acidophilus C7282 in feed supplementation on growth performance, Salmonella invasion, inflammation, and mediating signaling in broilers infected with Salmonella Typhimurium (S. Typhimurium). A total of 240 broilers at day old were randomly allocated into four groups, orally infected with S. Typhimurium and supplemented with individual or combined Lactobacilli DPP8 and C7282 at doses of 0 (control), 1010 (individual), or 2.0 × 1010 (combination) cfu/kg of diet for 21 d. The results showed that supplementing Lactobacilli improved (p 0.05) feed intake and body weight gain and decreased (p 0.05) S. Typhimurium load in the caecum, harder gland, spleen and bursa of Fabricius. Also, the supplements decreased (p 0.05) interleukin (1/2/4), tumor necrosis factor and interferon in the serum, enhanced (p 0.05) interleukin 10, and downregulated gene expressions of inflammatory mediators including Janus kinase (Jak2/3), signal transducer and activator of transcription protein (STAT3/4/5/6) in the intestinal mucosa. In contrast, diets containing DPP8 exhibited greater effects on the inhibition of the pathogen and inflammatory response than C7282. The obtained data suggest that Lactobacilli C7282 and DPP8 can be used as feed additives to inhibit colonization and translocation of S. Typhimurium and inflammatory responses via downregulating Jak/STAT signaling in broilers.
Assuntos
Animais , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Intoxicação Alimentar por Salmonella , Lactobacillus/química , Salmonella typhimuriumRESUMO
To investigate the protective effect of glutamine (Gln) on lymphocyte proliferation and the intestinal mucosal immune response in heat-stressed broilers, 360 21-day-old Arbor Acres (AA) broilers were assigned to 4 groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate for 21 days. The chickens were fed a basal diet under no stress (NS group), a basal diet under heat stress (HT group), or a basal diet under heat stress with the addition of either 0.5 % or 1.0 % Gln. The results showed that the broilers in the HT group exhibited fewer proliferating peripheral lymphocytes, a lower growth performance, phagocytic rate and index of neutrophils, fewer goblet cells in whole intestine and intraepithelial lymphocyte (IEL) cells in the ileum, a lower sIgA content in the duodenum and the jejunum, a lower immunoglobulin content of serum and intestinal mucosa, than those of the NS group (p<0.05). Diets supplemented with Gln increased growth performance, the number of proliferating peripheral lymphocytes, the phagocytic rate and phagocytic index of neutrophils, the number of whole intestine goblet cells and ileum IEL cells, the sIgA contents of the duodenum and the jejunum, and the immunoglobulin contents of serum and intestinal mucosa (p<0.05) in broilers exposed to HT. In conclusion, Gln can enhance intestinal immune function in broiler chickens by stimulating T and B lymphocyte proliferation, increasing the number of goblet cells and IEL cells, as well as increasing the content of sIgA and immunoglobulin secretion.
Assuntos
Animais , Galinhas/fisiologia , Galinhas/imunologia , Galinhas/microbiologia , Glutamina/análise , Imunidade nas Mucosas , Resposta ao Choque Térmico , LinfócitosRESUMO
To investigate the protective effect of glutamine (Gln) on lymphocyte proliferation and the intestinal mucosal immune response in heat-stressed broilers, 360 21-day-old Arbor Acres (AA) broilers were assigned to 4 groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate for 21 days. The chickens were fed a basal diet under no stress (NS group), a basal diet under heat stress (HT group), or a basal diet under heat stress with the addition of either 0.5 % or 1.0 % Gln. The results showed that the broilers in the HT group exhibited fewer proliferating peripheral lymphocytes, a lower growth performance, phagocytic rate and index of neutrophils, fewer goblet cells in whole intestine and intraepithelial lymphocyte (IEL) cells in the ileum, a lower sIgA content in the duodenum and the jejunum, a lower immunoglobulin content of serum and intestinal mucosa, than those of the NS group (p<0.05). Diets supplemented with Gln increased growth performance, the number of proliferating peripheral lymphocytes, the phagocytic rate and phagocytic index of neutrophils, the number of whole intestine goblet cells and ileum IEL cells, the sIgA contents of the duodenum and the jejunum, and the immunoglobulin contents of serum and intestinal mucosa (p<0.05) in broilers exposed to HT. In conclusion, Gln can enhance intestinal immune function in broiler chickens by stimulating T and B lymphocyte proliferation, increasing the number of goblet cells and IEL cells, as well as increasing the content of sIgA and immunoglobulin secretion.(AU)
Assuntos
Animais , Galinhas/imunologia , Galinhas/microbiologia , Galinhas/fisiologia , Glutamina/análise , Imunidade nas Mucosas , Resposta ao Choque Térmico , LinfócitosRESUMO
INTRODUCTION: Urothelial carcinoma (UC) is an aggressive malignancy and has a poor prognosis in the metastatic state. Treatment of UC remains a challenge, and as a first-line regimen for advanced UC, standard platinum-based chemotherapy is unfit for many patients due to numerous comorbidities and poor performance status. Recently, five immune checkpoint inhibitors have been approved for the treatment of patients with advanced UC who were ineligible for platinum-based regimens or suffered tumor progression in post-platinum setting. However, not long ago, the U.S. Food and Drug Administration restricted the use of two common immune checkpoint blockades, atezolizumab and pembrolizumab, due to uncertain survival benefit as mono-therapy. In this scenario, we reviewed rapidly surfacing clinical trials to assess the efficacy and safety of immunotherapy targeting the PD-1 pathway for advanced UC. METHODS: A comprehensive search was conducted in PubMed, EMBASE and Cochrane Library for all clinical trials where the efficacy and safety were reported. Our primary outcome was efficacy evaluated by objective response rate (ORR), 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate, and second outcome was safety assessed by any grade and grade 3-4 treatment-related adverse events (TRAEs). We chose percentages with 95% confidence intervals (CI) as the evaluation indexes and used a random-effects model to account for heterogeneity. RESULTS: We included 14 clinical trials with 2674 total patients in this meta-analysis. After removing unqualified studies on the basis of sensitivity analyses, 13 studies were pooled to evaluate the overall ORR, 8 studies for the 1-year OS rate and 6 studies for the 1-year PFS rate. The pooled data of ORR, 1-year OS rate, and 1-year PFS rate were 0.20 (95% CI 0.18-0.22, I2 = 38.4%, P = 0.078), 0.50 (95% CI 0.46-0.53, I2 = 30.3%, P = 0.186), and 0.17 (95% CI 0.14-0.20, I2 = 0.0%, P = 0.668), respectively. Similarly, 13 trials were utilized to compute the pooled rate of any-grade TRAEs. The pooled estimation of any-grade was 0.65 (95% CI 0.63-0.67, I2 = 1.7%, P = 0.429). The pooled rate of grade 3-4 TRAEs subgroups with Atezolizumab, Pembrolizumab, Durvalumab, Nivolumab and Avelumab were 0.11 (95% CI 0.06-0.15, I2 = 83.5%, P = 0.000), 0.15 (95% CI 0.13-0.18, I2 = 0.0%, P = 0.971), 0.06 (95% CI 0.03-0.09, I2 = 0.0%, P = 0.566), 0.19 (95% CI 0.15-0.23, I2 = 0.0%, P = 0.480) and 0.08 (95% CI 0.05-0.11, I2 = 0.0%, P = 0.702), respectively. CONCLUSION: This study showed that the immunotherapy targeting the PD-1 pathway had durable efficacy and acceptable safety in patients with advanced UC. The comprehensive role of immune checkpoint inhibitors in comparison to other treatments needs further confirmation basing on RCTs.
Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Urotélio/patologia , Ensaios Clínicos como Assunto , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Viés de Publicação , Neoplasias Urológicas/mortalidadeRESUMO
OBJECTIVE: Liver metastasis is one of the major causes of cancer-related death in patients with colorectal cancer (CRC). The purpose of this study was to identify specific molecules which are involved in colorectal liver metastasis (CRLM). MATERIALS AND METHODS: In this study, we employed TMT (tandem mass tags)-labeling combined with liquid chromatography-mass spectrometry technology to do comparative analyses of proteomics between the primary tumor specimens derived from colorectal cancer patients with or without liver metastasis. Pathway enrichment analyses were performed using DAVID database. The crucial molecules were identified through protein-protein interaction network. Immunohistochemistry (IHC) was employed to analyze the expression of THBS1 (thrombospondin-1) in CRC tissues. Finally, transwell cell migration and invasion assays were performed to explore the roles of THBS1 in CRC cell migration and invasion. RESULTS: We found that the expression of 311 proteins was dysregulated in CRLM using quantitative proteomics. Among these proteins, we identified FN1, TIMP1, THBS1, POSTN and VCAN as five crucial proteins in CRLM by analysis in silico. IHC assay revealed that increased THBS1 expression was significantly correlated with liver metastasis as well as poor prognosis of CRC patients. GEO data analysis also suggests that upregulated mRNA level of THBS1 is also associated with shorter overall survival of CRC patients. Moreover, THBS1 depletion inhibited migration and invasion of CRC cells through attenuating epithelial-mesenchymal transition. Co-expression analyses with TCGA data indicated that THBS1 is co-expressed with mesenchymal markers, including Vimentin, N-cadherin, Snail1 and Twist1 in CRC tissues. CONCLUSIONS: By collecting the omics data with functional studies, the present results reveal that THBS1 facilitates colorectal liver metastasis through promoting epithelial-mesenchymal transition. This understanding of molecular roles of THBS1 in CRLM may be promising to develop targeted therapies to prolong survival in CRC patients.
Assuntos
Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/secundário , Trombospondina 1/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/mortalidade , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Mapas de Interação de ProteínasRESUMO
PURPOSE: Epithelial to mesenchymal transition (EMT) plays an important role in acquired resistance to gefitinib in lung cancer. This study aimed to explore the underlying mechanism of gefitinib-induced EMT in lung adenocarcinoma cells harboring EGFR mutation. METHODS: CXC chemokine receptor 4 (CXCR4) expression was determined through qRT-PCR, Western blot and flow cytometry assays in lung cancer cell line (PC9) bearing mutated EGFR. Functional role of CXCR4 was inhibited applying siRNAs as well as the specific antagonist AMD3100. The expression of EMT markers was determined, and the migration of PC9 cells was measured with transwell assay. RESULTS: We found that gefitinib promoted the migratory capacity of PC9 cells in vitro, which correlated with EMT occurrence through upregulation of CXCR4. Blocking CXCR4 significantly suppressed gefitinib-induced enhancement of migration and EMT. Moreover, we determined that the upregulation of CXCR4 by gefitinib was dependent on TGF-ß1/Smad2 signaling activity. CONCLUSIONS: Our study suggested a potential mechanism by which gefitinib induced EMT in cells harboring EGFR mutation through a pathway involving TGF-ß1 and CXCR4. Thus, the combination of CXCR4 antagonist and TGFßR inhibitors might provide an alternative strategy to overcome progression of lung cancer after gefitinib treatment.
Assuntos
Adenocarcinoma de Pulmão/patologia , Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/genética , Gefitinibe/farmacologia , Neoplasias Pulmonares/patologia , Receptores CXCR4/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adenocarcinoma de Pulmão/genética , Benzilaminas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Ciclamos/farmacologia , Humanos , Neoplasias Pulmonares/genética , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno/farmacologia , Receptores CXCR4/antagonistas & inibidores , Proteína Smad2/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Surgery is becoming more practical and effective than conservative treatment in improving the poor outcomes of patients with breast cancer liver metastasis (BCLM). However, there is no generally acknowledged set of standards for identifying BCLM candidates who will benefit from surgery. METHODS: Between January 2011 and September 2018, 67 female BCLM patients who underwent partial hepatectomy were selected for analysis in the present study. Prognostic factors after hepatectomy were determined. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and intrahepatic recurrence-free survival (IHRFS). RESULTS: The 1-, 3- and 5-year OS of patients treated with surgery was 93.5%, 73.7% and 32.2%, respectively, with a median survival time of 57.59 months. The Pringle manoeuvre [hazard radio (HR) = 0.117, 95% CI0.015-0.942, p = 0.044] and an increased interval between breast surgery and BCLM diagnosis (HR0.178, 95% CI 0.037-0.869, p = 0.033) independently predicted improved overall survival for BCLM patients. The 1-, 2- and 3-year IHRFS of patients who underwent surgery was 62.8, 32.6% and 10.9%, respectively, with a median intrahepatic recurrence-free survival time of 13.47 months. Moderately differentiated tumours (HR 0.259, 95% CI 0.078-0.857, p = 0.027) and the development of liver metastasis more than 2 years after breast surgery (HR 0.270, 95% CI 0.108-0.675, p = 0.005) might be predictors of increased IHRFS. CONCLUSIONS: An interval of more than 2 years between breast cancer surgery and liver metastasis seems to be an indication of liver surgery in BCLM patients. The Pringle manoeuvre and moderately differentiated tumours are potential predictors associated with OS and IHRFS, respectively, as benefits from liver resection. Studies with increased sample sizes are warranted to validate our results.
Assuntos
Neoplasias da Mama/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The aim of this study was to investigate the effects of glutamine (Gln) on the intestinal mucosal structure and immune cells of broilers infected with Salmonella Enteritidis. 160 1-d-old commercial Arbor Acres (AA) broilers were randomly selected to receive one of four treatments, each of which had 5 replicates. Each replicate consisted of 8 chicks subjected to a 21-d feeding trial. Group I served as the unchallenged (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. The birds in groups III and IV were treated with 0.5% and 1.0% Gln. The results showed that S. Enteritidis infection led to a decrease in the relative length and weight, villus height:crypt depth (VH:CD) of the jejunum and ileum, the number of intraepithelial lymphocyte cells, and number of goblet cells and an increase in the number of mast goblet cells compared with the measurements of these parameters in the CON group (p 0.05). In addition, the Gln groups had increased relative length and weight, VH:CD of the jejunum and ileum, numbers of intraepithelial lymphocyte cells, and numbers of goblet cells and decreased crypt depth in the jejunum and ileum and numbers of mast goblet cells compared with the measurements of these parameters in the SCC group (p 0.05). It was concluded that Gln added to broiler diets can effectively alleviate the intestinal mucosal damage caused by S. Enteritidis infection and improve its normal defense barrier function.(AU)
Assuntos
Animais , Galinhas/microbiologia , Salmonella enteritidis/patogenicidade , Glutamina/análise , Microbioma GastrointestinalRESUMO
The aim of this study was to investigate the effects of glutamine (Gln) on the intestinal mucosal structure and immune cells of broilers infected with Salmonella Enteritidis. 160 1-d-old commercial Arbor Acres (AA) broilers were randomly selected to receive one of four treatments, each of which had 5 replicates. Each replicate consisted of 8 chicks subjected to a 21-d feeding trial. Group I served as the unchallenged (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. The birds in groups III and IV were treated with 0.5% and 1.0% Gln. The results showed that S. Enteritidis infection led to a decrease in the relative length and weight, villus height:crypt depth (VH:CD) of the jejunum and ileum, the number of intraepithelial lymphocyte cells, and number of goblet cells and an increase in the number of mast goblet cells compared with the measurements of these parameters in the CON group (p 0.05). In addition, the Gln groups had increased relative length and weight, VH:CD of the jejunum and ileum, numbers of intraepithelial lymphocyte cells, and numbers of goblet cells and decreased crypt depth in the jejunum and ileum and numbers of mast goblet cells compared with the measurements of these parameters in the SCC group (p 0.05). It was concluded that Gln added to broiler diets can effectively alleviate the intestinal mucosal damage caused by S. Enteritidis infection and improve its normal defense barrier function.
Assuntos
Animais , Galinhas/microbiologia , Glutamina/análise , Microbioma Gastrointestinal , Salmonella enteritidis/patogenicidadeRESUMO
The objective of the study was to investigate the mechanism by which dietary energy concentration regulates laying performance in geese. Eighty 558-day-old female Sichuan White geese were randomly allotted to two dietary treatments, each treatment was fed 1 of 2 experimental diets containing 10.00 (deficient) or 11.80MJ/kg metabolizable energy (sufficient) for 30 days. Laying performance, hormone concentration and gene expressions in hypothalamus-pituitary-gonadal axis were examined in geese. Birds fed the sufficient-energy diet had significantly higher average egg weight, daily laying rate, and lower feed to egg ratio than those fed the deficient-energy (p 0.05). The birds fed sufficient-energy diet had higher concentration of serum insulin like growth factor 1 (IGF-1), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and estradiol (E2) than those in deficient-energy diet (p 0.05). The mRNA expression levels of GnRH in the hypothalamus, FSH in the pituitary and E2 in the ovary of birds fed sufficient-energy diet were higher than the corresponding counterpart in deficient-energy diet (p 0.05), respectively. In conclusion, the study implied that dietary energy modifies laying possibly through regulating reproductive hormone secretion and gene expression in hypothalamus-pituitary-gonad axis in laying geese.
Assuntos
Animais , Expressão Gênica , Gansos/fisiologia , Gansos/metabolismo , Hormônios Esteroides Gonadais , Gônadas , Hipotálamo , HipófiseRESUMO
The aim was to investigate the effect of glutamine (Gln) on broilers challenged with Salmonella Enteritidis. 240 1-day-old birds were divided into four groups in a completely randomized design, each of which included 6 replicates with 10 birds per replicate. Group I served as the unchallenged, untreated control (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. Birds in group III and IV were treated with 0.5% (Gln 1) and 1.0% (Gln 2), respectively, of Gln. The results indicated that S. Enteritidis infection led to a decrease in the average body weight at d 7, 14, and 21 (p 0.05). Chickens fed the Gln showed improved average body weights in comparison with the SCC group (p 0.05). At d 4, 7, 14, and 21, the Gln groups increased digestive enzyme (trypsin, lipase and amylase (except the amylase activity of jejunum at d 14 and d 21)) activities in the intestine (p 0.05), superoxide dismutase (SOD) (at d 14 jejunum; except at d 4, ileum) and catalase (CAT) (at d 4, and d 21, jejunum; d 4, ileum) activity in the serum (except at d 14) and intestinal mucosa (p 0.05), and the mRNA expression of SOD, CAT and nuclear respiratory factor 2 (Nrf2) of the intestinal mucosa compared with the SCC group (p 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of S. Enteritidis infection of broilers.
Assuntos
Animais , Galinhas/fisiologia , Galinhas/metabolismo , Glutamina/análise , Glutamina/efeitos adversos , Salmonella enteritidis , OxirreduçãoRESUMO
The objective of the study was to investigate the mechanism by which dietary energy concentration regulates laying performance in geese. Eighty 558-day-old female Sichuan White geese were randomly allotted to two dietary treatments, each treatment was fed 1 of 2 experimental diets containing 10.00 (deficient) or 11.80MJ/kg metabolizable energy (sufficient) for 30 days. Laying performance, hormone concentration and gene expressions in hypothalamus-pituitary-gonadal axis were examined in geese. Birds fed the sufficient-energy diet had significantly higher average egg weight, daily laying rate, and lower feed to egg ratio than those fed the deficient-energy (p 0.05). The birds fed sufficient-energy diet had higher concentration of serum insulin like growth factor 1 (IGF-1), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and estradiol (E2) than those in deficient-energy diet (p 0.05). The mRNA expression levels of GnRH in the hypothalamus, FSH in the pituitary and E2 in the ovary of birds fed sufficient-energy diet were higher than the corresponding counterpart in deficient-energy diet (p 0.05), respectively. In conclusion, the study implied that dietary energy modifies laying possibly through regulating reproductive hormone secretion and gene expression in hypothalamus-pituitary-gonad axis in laying geese.(AU)