Résumé
Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.
Sujets)
Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Quinazolines/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Irradiation crânienne/méthodes , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Bévacizumab/usage thérapeutique , Tumeurs du poumon/anatomopathologie , Antinéoplasiques/usage thérapeutique , Facteurs temps , Analyse de variance , Résultat thérapeutique , Géfitinib , MutationRésumé
Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.
Sujets)
Humains , Antiviraux/pharmacologie , Entérovirus humain A/effets des médicaments et des substances chimiques , Naphtoquinones/pharmacologie , Rhabdomyosarcome/virologie , Technique de Western , Lignée cellulaire tumorale , Cytokines/analyse , Relation dose-effet des médicaments , Réaction de polymérisation en chaine en temps réel , Tests de toxicité , Méthode des plages virales , Réplication virale/effets des médicaments et des substances chimiquesRésumé
OBJECTIVES: Although more and more video‑assisted thoracoscopic surgery (VATS) lobectomies via two‑port have been performed to treat early‑stage nonsmall‑cell lung cancer (NSCLC) in recent years, concern remains whether it can achieve satisfactory adequacy of lymphadenectomy. This retrospective study was aimed to evaluate the adequacy of lymphadenectomy by VATS via two‑port, compared with three‑port. MATERIALS AND METHODS: The clinical and pathological data of patients who underwent VATS lobectomy via two‑port or three‑port with systematic lymphadenectomy for clinical early‑stage NSCLC were reviewed. As the main evaluation criterion, the number of mediastinal nodes and node stations, and the total number of nodes and node stations was compared by approach. RESULTS: 1872 patients with NSCLC underwent VATS lobectomy, 1086 via a two‑port approach and 786 through a three‑port approach. In the two‑port and three‑port groups, the baseline patient characteristics were similar, and there was no significant difference in the mean number of dissected mediastinal lymph nodes (MLNs) (12.3 ± 2.2 and 13.1 ± 1.7, P > 0.05) and the mean number of dissected MLN stations (3.5 ± 0.7 and 3.4 ± 0.8, P > 0.05). Meanwhile, the mean total number of dissected lymph nodes (24.1 ± 4.2 and 25.7 ± 4.3, P > 0.05) and the mean total number of dissected lymph node stations (6.8 ± 1.3 and 6.9 ± 1.1, P > 0.05) were also similar. Otherwise, in terms of postoperative complications, there was no obvious difference in the two groups. CONCLUSIONS: The adequacy of lymphadenectomy including MLN dissection by VATS via two‑port is similar to that via three‑port for patients undergoing lobectomy for clinical early‑stage NSCLC.
Résumé
Glycosylation of proteins is an essential process in all eukaryotes. Mucin‑type O‑linked glycosylation is an evolutionarily conserved protein modification as a kind of glycosylation of proteins. The role of O‑glycosylation was well documented in multiple cancers. While in breast cancer, the enzymes that catalyzed the initiation of O‑glycosylation remained elusive. In this review, we briefly introduced the process of the initiation of O‑glycosylation and summarized the roles of enzymes that catalyzed the initiation step of O‑glycosylation in the breast cancer carcinogenesis, development, and progression. Finally, we summarized some attempts exploring the therapy against aberrant O‑glycosylation.
Résumé
BACKGROUND: Diaphragmatic dysfunction and its negative physiologic disadvantages are less commonly reported in patients with lung cancer video‑assisted thoracoscopic lobectomy. The aim of this study was to investigate the outcomes of this complication on pulmonary function and quality‑of‑life in patients following video‑assisted thoracoscopic lobectomy. OBJECTIVES: The aim of this study was to investigate potential benefits on pulmonary function and quality‑of‑life with normal diaphragmatic motion. MATERIALS AND METHODS: A retrospective study was conducted in 64 patients with nonsmall cell lung cancer after video‑assisted thoracoscopic lobectomy. The population were divided into groups 1 (with diaphragmatic paralysis, n = 32) and group 2 (without diaphragmatic paralysis, n = 32) according diaphragmatic motion after postoperatively 6 months. And then, we investigated the difference between the two groups on pulmonary function and quality‑of‑life. RESULTS: (1) At 6 months after resection, the patients in group 1 had lost 25% of their preoperative forced expiratory volume in the 1 s (FEV1) (P < 0.001), and the patients in group 2 had lost 15% of their preoperative FEV1 (P < 0.001). And the other spirometric variables in group 1 were significantly worse than that of group 2 (P < 0.001). (2) The most frequently reported postoperative symptoms were fatigue, coughing, dyspnea, and thoracotomy pain in two groups. Of all the symptom scales, only the dyspnea scale showed a significant difference which subject has a higher proportion and scale compared to control. CONCLUSIONS: The present study indicates that unilateral diaphragmatic paralysis following video‑assisted thoracoscopic lobectomy caused adverse effects on postoperative pulmonary function and quality‑of‑life.
Sujets)
Carcinome à petites cellules/chirurgie , Muscle diaphragme/physiologie , Humains , Poumon/physiologie , Tumeurs du poumon/chirurgie , Pneumonectomie , Qualité de vie , Tests de la fonction respiratoire , Études rétrospectives , Chirurgie thoracique vidéoassistée , ThoracoscopieRésumé
In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.
Sujets)
Humains , Cellules épithéliales/effets des médicaments et des substances chimiques , /métabolisme , Norépinéphrine/pharmacologie , Transduction du signal/physiologie , Lignée cellulaire , Test ELISA , Cellules épithéliales/métabolisme , Muqueuse gastrique/effets des médicaments et des substances chimiques , Muqueuse gastrique/métabolisme , Régulation de l'expression des gènes/physiologie , /génétique , Facteur de transcription NF-kappa B/métabolisme , Norépinéphrine/métabolisme , Réaction de polymérisation en chaine en temps réel , ARN messager/métabolisme , Récepteurs bêta-adrénergiques/métabolisme , Facteurs de transcription/physiologie , Régulation positiveRésumé
MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1 , p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.
Sujets)
Humains , Apoptose/effets des médicaments et des substances chimiques , Benzofuranes/administration et posologie , Endophytes/composition chimique , Points de contrôle de la phase G1 du cycle cellulaire/effets des médicaments et des substances chimiques , Xylariales/composition chimique , Protéines régulatrices de l'apoptose/génétique , Benzofuranes/isolement et purification , Protéines du cycle cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , /effets des médicaments et des substances chimiques , /effets des médicaments et des substances chimiques , Protéines de liaison à l'ADN/effets des médicaments et des substances chimiques , Cytométrie en flux , Facteurs de transcription Forkhead/effets des médicaments et des substances chimiques , Cycadopsida , /effets des médicaments et des substances chimiques , Cellules HeLa , Protéines nucléaires/effets des médicaments et des substances chimiques , Réaction de polymérisation en chaine en temps réel , Transcription génétique , Facteurs de transcription/effets des médicaments et des substances chimiques , Protéines suppresseurs de tumeurs/effets des médicaments et des substances chimiquesRésumé
The tissue inhibitor of metalloproteinases (TIMP)-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs) but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line), L-02 (a normal liver cell line) and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma) using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60 percent and reduced the migration to about 30 percent. Meanwhile, our data showed that interleukin-6 (IL-6) (100 ng/mL) could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.