RÉSUMÉ
OBJECTIVE: To explore the efficacy of high tibial osteotomy ï¼HTOï¼ combined with medial meniscus centralization in knee osteoarthritis. METHODS: A total of 26 patients who underwent surgery from October 2018 to October 2020 were reviewed. Among them, 14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group, including 8 males and 6 females, with an average age of ï¼50.2±1.4ï¼ years old and follow-up time of ï¼16.8±4.0ï¼ months. Twelve patients with high tibial osteotomy were in the control group, including 6 males and 6 females, with an average age of ï¼50.9±1.8ï¼ years and follow-up time of ï¼19.0±4.8ï¼ months. Operation time, the knee Lysholm score, knee 2000 IKDC score, MRI, femoral tibial angleï¼FTAï¼, hip knee ankle angle ï¼HKAï¼, and intraoperative and postoperative complications were recorded. RESULTS: All the incisions healed without any complication. The operation time in the centralized group was longer than that in the control group[ï¼65.0±2.1ï¼min vsï¼52.0±2.1ï¼min, P<0.05]. The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[ï¼2.8±1.4ï¼ mm vs ï¼1.1±2.2ï¼ mm, P<0.05]. The FTA, HKA, knee Lyshlom score, and 2000 IKDC score between two groups were no significantly ï¼P>0.05ï¼. Postoperative knee Lyshlom score and knee 2000 IKDC score improved in both groupsï¼P<0.05ï¼. CONCLUSION: HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function. The medium and long-term curative effect still needs long-term follow-up of more cases.
Sujet(s)
Gonarthrose , Mâle , Femelle , Humains , Adulte d'âge moyen , Gonarthrose/chirurgie , Ménisques de l'articulation du genou/chirurgie , Résultat thérapeutique , Articulation du genou/chirurgie , Tibia/chirurgie , Ostéotomie , Études rétrospectivesRÉSUMÉ
OBJECTIVE: We searched for a predictive biomarker that also predicts whether patients would benefit from immune checkpoint blockade (ICB) treatment from a few angles, because existing biomarkers no longer wholly replicate the interconnections of distinctive elements in the tumor microenvironment (TME). METHODS: We identified 55 pivotal IRGs by performing a WGCNA and univariate Cox regression analysis on a lung adenocarcinoma dataset from the TCGA database. The IRGPI model was then constructed using multivariate Cox regression analysis, which identified 16 genes and verified the use of the GSE68465 database. The AUC of the IRGPI was compared to those of the current biomarkers to determine its predictive potential. Then we examined the molecular and immunological properties of ICB and assessed its effectiveness using CTLA4 expression and TIDE. RESULTS: Patients with a high IRGPI had a later clinical stage, more severe symptoms, and a worse prognosis. Patients with a low IRGPI had a higher immune escape potential and were less responsive to immunotherapy. CONCLUSION: The IRGPI may be a biomarker for determining the prognosis of patients and whether they respond favorably to ICB therapy.
RÉSUMÉ
Locus coeruleus (LC) is a small nucleus located deep in the brainstem that contains the majority of central noradrenergic neurons, which provide the primary source of noradrenaline (NA) throughout the entire central nervous system (CNS).The release of neurotransmitter NA is considered to modulate arousal, sensory processing, attention, aversive and adaptive stress responses as well as high-order cognitive function and memory, with the highly ramified axonal arborizations of LC-NA neurons sending wide projections to the targeted brain areas. For over 30 years, LC was thought to be a homogeneous nucleus in structure and function due to the widespread uniform release of NA by LC-NA neurons and simultaneous action in several CNS regions, such as the prefrontal cortex, hippocampus, cerebellum, and spinal cord. However, recent advances in neuroscience tools have revealed that LC is probably not so homogeneous as we previous thought and exhibits heterogeneity in various aspects. Accumulating studies have shown that the functional complexity of LC may be attributed to its heterogeneity in developmental origin, projection patterns, topography distribution, morphology and molecular organization, electrophysiological properties and sex differences. This review will highlight the heterogeneity of LC and its critical role in modulating diverse behavioral outcomes.
Sujet(s)
Locus ceruleus , Neurones , Femelle , Mâle , Humains , Locus ceruleus/anatomie et histologie , Locus ceruleus/physiologie , Neurones/physiologie , Moelle spinale , Encéphale , NorépinéphrineRÉSUMÉ
Quantum teleportation plays a significant role in the field of quantum communication. This paper investigates quantum teleportation through a noisy environment by using GHZ state and non-standard W state as quantum channels. We analyze the efficiency of quantum teleportation by solving analytically a master equation in Lindblad form. Following the quantum teleportation protocol, we obtain the fidelity of quantum teleportation as a function of evolution time. The calculation results show that the teleportation fidelity using non-standard W is higher in comparison to GHZ state at the same evolution time. Moreover, we consider the efficiency of teleportation with weak measurements and reverse quantum measurement under amplitude damping noise. Our analysis suggests that the teleportation fidelity using non-standard W is also more robust to noise than GHZ state in the same conditions. Interestingly, we found that weak measurement and its reverse operation have no positive effect on the efficiency of quantum teleportation by using GHZ and non-standard W state in the amplitude damping noise environment. In addition, we also demonstrate the efficiency of quantum teleportation can be improved by making minor modifications to the protocol.
RÉSUMÉ
OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.
Sujet(s)
Cirrhose biliaire , Souris , Animaux , Cirrhose biliaire/traitement médicamenteux , Cirrhose biliaire/métabolisme , Cellules de Küpffer/métabolisme , Sulfates , Inflammation , Lipopolysaccharides/pharmacologie , Tyrosine , Clostridium , PhénylalanineRÉSUMÉ
During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
Sujet(s)
COVID-19 , Analyse du sperme , Vaccins contre la COVID-19 , Femelle , Humains , Mâle , Grossesse , Études rétrospectives , Sperme , Numération des spermatozoïdes , Mobilité des spermatozoïdes , Spermatozoïdes , Vaccination , Vaccins inactivésRÉSUMÉ
INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.
RÉSUMÉ
The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
Sujet(s)
Carcinome pulmonaire non à petites cellules/génétique , Tumeurs du poumon/génétique , Marqueurs biologiques tumoraux/génétique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Cisplatine/usage thérapeutique , Survie sans rechute , Récepteurs ErbB/génétique , Géfitinib/usage thérapeutique , Génomique , Humains , Tumeurs du poumon/traitement médicamenteuxRÉSUMÉ
Chromosome 7 plays an important role in lung tumorigenesis. Chromosome 7 copy number changes might be an early event of lung cancer tumorigenesis. Here we investigate whether chromosome 7p copy number gain is a detectable genetic event with plasma cell-free DNA for early lung cancer detection. Eighteen surgical eligible lung cancer patients and eighteen non-cancer controls were recruited. Peripheral blood was collected before surgery. Cell-free DNA was profiled with low coverage whole-genome sequencing. Chromosome 7 copy number gains were defined as chr7 normalized coverage ≥1.0005 and p-value <0.05. Plasma cell-free DNA chr7 copy gains were then compared to pathological examinations on surgical tissues. 83.3% of patients were confirmed as malignancy post-operation, 12 patients with adenocarcinoma, and 3 with squamous-carcinoma. The other 16.7% were benign lesions. Cell-free DNA was successfully extracted from pre-surgical plasma samples, with a concentration range from 0.18 to 0.49 ng/µl. Chromosome 7 short arm copy gains were found in 66.7% (10/15) patients, including 66.7% (4/6) T1aN0M0 and 50.0% (1/2) Tis patients, otherwise, chr7p gain was found in 0% (0/3) benign lesions. The specificity was further examined in 18 volunteers who undergoing routine body examinations. Meanwhile, positive carcinoembryonic antigen (CEA) and cytokeratin-19-fragment (CYFRA21-1) were only found in 1/18 (5.7%) and 4/18 (22.2%), respectively. Taking together, Ultrasensitive- Chromosomal Aneuploidy Detector (UCAD) chr7p or UCAD chr7p and tumor biomarker positivity can predict 12/15 (80%, 95% CI: 49.0-94.3%) early lung cancers. Further analyses showed that chr7p copy number gains tend to be enriched in normal EGFR/KRAS patients (Fisher's test, p-value = 0.077). Chromosome 7p copy gain is a useful peripheral blood tumor biomarker from lung cancer detection.
Sujet(s)
Acides nucléiques acellulaires , Tumeurs du poumon , Antigènes néoplasiques , Acides nucléiques acellulaires/génétique , Chromosomes , Variations de nombre de copies de segment d'ADN , Humains , Kératine-19 , Poumon , Tumeurs du poumon/diagnostic , Tumeurs du poumon/génétique , Études prospectivesRÉSUMÉ
The tumor suppressor protein p53 plays important roles in DNA repair, cell cycle and genetic stability. In the present study, a p53 gene in the mud crab (Scylla paramamosain) (designated as Sp-53) was identified and characterized. The open reading frame of Sp-53 was comprised a 1383 bp, which encoded a putative protein of 460 amino acids. Sp-53 is expressed in all examined tissues, with the highest expression in hepatopancreas and hemocytes. Vibrio parahaemolyticus infection induced oxidative stress, and led to DNA damage. The Sp-53 transcriptions in hepatopancreas were significantly up-regulated after V. parahaemolyticus infection. RNA interference (RNAi) experiment was used to understand the roles of Sp-53 in response to V. parahaemolyticus infection. Knocking down Sp-53 in vivo significantly reduced the expression of the Mn-SOD, Gpx3 and caspase 3 after V. parahaemolyticus infection. Moreover, the mortality of mud crabs and DNA damage in Sp-53-silenced mud crab challenged with V. parahaemolyticus were significantly higher than those in the control group. All these results suggested that Sp-53 played an important role in responses to V. parahaemolyticus infection through its participation in regulation of antioxidant defense, DNA repair and apoptosis.
Sujet(s)
Brachyura/métabolisme , Brachyura/microbiologie , Protéine p53 suppresseur de tumeur/métabolisme , Vibrio parahaemolyticus/physiologie , Séquence d'acides aminés , Animaux , Séquence nucléotidique , Clonage moléculaire , Altération de l'ADN , Interactions hôte-pathogène , PhylogenèseRÉSUMÉ
BACKGROUND: The clinical significance of signet ring cells (SRCs) in surgical esophageal and esophagogastric junction adenocarcinoma (EEGJA) remains unclear now. AIM: To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies. METHODS: The PubMed, Web of Science, and EMBASE electronic databases were searched for the relevant literature up to March 28, 2021. The relative risk (RR) with 95% confidence interval (CI) was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients, and the hazard ratio (HR) with 95%CI was calculated to explore the impact of SRC on the prognosis. All statistical analyses were conducted with STATA 12.0 software. RESULTS: A total of ten articles were included, involving 30322 EEGJA patients. The pooled results indicated that the presence of SRCs was significantly associated with tumor location (RR: 0.76, 95%CI: 0.61-0.96, P = 0.022; I 2 = 49.4%, P = 0.160) and tumor-node-metastasis stage (RR: 1.30, 95%CI: 1.02-1.65, P = 0.031; I 2 = 73.1%, P = 0.002). Meanwhile, the presence of SRCs in surgical EEGJA patients predicted a poor overall survival (HR: 1.36, 95%CI: 1.12-1.65, P = 0.002; I 2 = 85.7%, P < 0.001) and disease-specific survival (HR: 1.86, 95%CI: 1.55-2.25, P < 0.001; I 2 = 63.1%, P = 0.043). CONCLUSION: The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients. However, more high-quality studies are still needed to verify the above findings.
RÉSUMÉ
PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.
Sujet(s)
Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Cisplatine/usage thérapeutique , Géfitinib/usage thérapeutique , Tumeurs du poumon/traitement médicamenteux , Mutation , Vinorelbine/usage thérapeutique , Adulte , Sujet âgé , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/mortalité , Carcinome pulmonaire non à petites cellules/anatomopathologie , Traitement médicamenteux adjuvant , Chine , Cisplatine/effets indésirables , Survie sans rechute , Récepteurs ErbB/génétique , Femelle , Géfitinib/effets indésirables , Humains , Tumeurs du poumon/génétique , Tumeurs du poumon/mortalité , Tumeurs du poumon/anatomopathologie , Mâle , Adulte d'âge moyen , Stadification tumorale , Facteurs temps , Vinorelbine/effets indésirablesRÉSUMÉ
OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, pâ¯=⯠0.019; LCSS, 1.13, 1.04-1.22, pâ¯=⯠0.003; TOI, 88.39, 4.40-1775.05, pâ¯=⯠0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, pâ¯=⯠0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, pâ¯=⯠0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, pâ¯=⯠0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Traitement médicamenteux adjuvant , Cisplatine/usage thérapeutique , Récepteurs ErbB/génétique , Géfitinib/usage thérapeutique , Humains , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Mutation , Stadification tumorale , Qualité de vie , Vinorelbine/usage thérapeutiqueRÉSUMÉ
Budd-Chiari syndrome (BCS) is an uncommon disorder defined as an obstruction of the hepatic venous outflow. Percutaneous transluminal balloon angioplasty is a less invasive treatment option for BCS patients. However, there are no reports regarding inferior vena cava (IVC) rupture caused by perforation route through a collateral vein during treatment of BCS. Here, we report a male patient with BCS who had a long segmental obstruction of the IVC and its collateral vessels. Here, IVC rupture occurred at the distal end of the obstructed IVC during a percutaneous angioplasty; the rupture was repaired successfully with an endovascular stent graft.
Sujet(s)
Angioplastie par ballonnet/effets indésirables , Syndrome de Budd-Chiari/thérapie , Lésions du système vasculaire/étiologie , Veine cave inférieure/traumatismes , Prothèse vasculaire , Implantation de prothèses vasculaires/instrumentation , Syndrome de Budd-Chiari/imagerie diagnostique , Femelle , Humains , Mâle , Adulte d'âge moyen , Endoprothèses , Résultat thérapeutique , Lésions du système vasculaire/imagerie diagnostique , Lésions du système vasculaire/chirurgie , Veine cave inférieure/imagerie diagnostique , Veine cave inférieure/chirurgieRÉSUMÉ
Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5-year relative survival rate is no more than 1%. Dysregulation of components of striatin-interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT-PCR (qRT-PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC-A1 cells and depleted STRIP2 in Calu-3 cells. Cell proliferation was evaluated by Cell Counting Kit-8 and colony-forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu-3 cells, and overexpression of STRIP2 had the opposite effects in SPC-A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p-Akt and phosphorylated-mammalian target of rapamycin (p-mTOR) in Calu-3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC-A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E-cadherin and reduced levels of N-cadherin, Vimentin and matrix metalloproteinase-9 in Calu-3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC-A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial-mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.
Sujet(s)
Adénocarcinome pulmonaire/métabolisme , Protéines du cytosquelette/génétique , Adénocarcinome/génétique , Adénocarcinome pulmonaire/génétique , Cadhérines/génétique , Cadhérines/métabolisme , Cycle cellulaire/génétique , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire/génétique , Protéines du cytosquelette/métabolisme , Transition épithélio-mésenchymateuse/génétique , Matrice extracellulaire/génétique , Régulation de l'expression des gènes tumoraux/génétique , Humains , Poumon/anatomopathologie , Tumeurs du poumon/génétique , Invasion tumorale/génétique , Phosphoric monoester hydrolases/génétique , Phosphoric monoester hydrolases/métabolisme , Vimentine/génétiqueRÉSUMÉ
Ubiquitin-specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non-small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down-stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.
Sujet(s)
Carcinome pulmonaire non à petites cellules/métabolisme , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/métabolisme , Tumeurs du poumon/anatomopathologie , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal , Ubiquitin thiolesterase/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaire , Stabilité enzymatique , Humains , Phosphohydrolase PTEN/métabolisme , PronosticRÉSUMÉ
BACKGROUND: The detection rate of ground-glass opacity (GGO) in young patients has increased year by year with the increasingly widespread use of high-resolution computed tomography (HRCT) and the increased resolution of HRCT imaging. However, no scholars have reported the clinical characteristics and prognosis of GGO in young patients systematically. The purpose of this study is to investigate the clinical characteristics and prognosis presenting as GGO in young patients. METHODS: Clinical data of 127 young patients who were diagnosed as GGO and who underwent video-assisted thoracoscopic surgery (VATS) and had routine pathological examination were collected from January 2016 to January 2017. Nodules were classified according to benign and malignant: 26 benign nodules (Group A) and 115 malignant nodules (Group B). The pathological types, nodules size, surgical methods were analyzed, and the clinical characteristics and prognosis were evaluated. RESULTS: The results of pathological examination of 91 pure ground-glass opacities (pGGOs) revealed 16 adenocarcinoma in situs (AISs), 42 micro invasive adenocarcinomas (MIAs), 13 invasive adenocarcinomas (IAs), 8 atypical adenomatous hyperplasias (AAHs), 1 inflammatory granuloma, 2 pulmonary inflammatory pseudotumors (IPTs) and 9 other benign nodules. The results of pathological examination of 50 mixed ground-glass opacities (mGGOs) revealed 6 AISs, 29 MIAs, 9 IAs, 1 AAH, 2 inflammatory granulomas and 3 other benign nodules. All patients had no lymph nodes invasion. The rates of perioperative complications were 6.30%, compared to 7.63% for long-term complications. None of the patients with GGO experienced a recurrence and death [2-year recurrence-free survival (RFS), 100%; 2-year overall survival (OS), 100%]. CONCLUSIONS: The GGO in young patients that received VATS has a high proportion of malignant, its prognosis is satisfied.
RÉSUMÉ
BACKGROUND: Circulating tumor cell (CTC) isolation methods based on nanostructured substrates can be used to isolate tumor cells from peripheral blood. This study aimed to validate the clinical application of our method and determine the appropriate diagnostic critical value. METHODS: AFM was used to detect the surface roughness of nanostructured substrates. Cell lines and blood samples were used to verify CTC isolation methods. The ROC curve and AUC were used to evaluate the diagnostic value of CTC numbers. RESULTS: First, AFM, cell binding yields, and tumor cell detection rate from blood showed that NS has a potential for cell adsorption. Then, the CTC detection method was verified by using cell lines and blood samples. The number of CTCs in patients with cancers or metastases were significantly greater than those of patients without cancers. Then, the ROC curves and AUC showed that this method had a medium diagnostic value. CONCLUSIONS: Isolating CTCs based on nanostructured substrates was appropriate for the clinical diagnosis of tumors, and samples with more than 1.5 CTCs/1 mL blood could be identified as CTC-positive.
Sujet(s)
Nanostructures , Tumeurs/diagnostic , Cellules tumorales circulantes , Hémogramme , Études cas-témoins , Femelle , Humains , Cellules MCF-7 , Mâle , Adulte d'âge moyen , Tumeurs/sangRÉSUMÉ
INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.