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1.
Zhonghua Zhong Liu Za Zhi ; 45(6): 455-463, 2023 Jun 23.
Article in Chinese | MEDLINE | ID: mdl-37355463

ABSTRACT

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.


Subject(s)
Adenocarcinoma , Lung Neoplasms , Multiple Pulmonary Nodules , Humans , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Lung/pathology , Tomography, X-Ray Computed
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(9): 1295-1301, 2022 Sep 06.
Article in Chinese | MEDLINE | ID: mdl-36207894

ABSTRACT

Objective: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , Antibodies, Viral , COVID-19/prevention & control , Fatigue , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Vaccination
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(9): 942-946, 2020 Sep 06.
Article in Chinese | MEDLINE | ID: mdl-32907282

ABSTRACT

Objective: Aanalysis the effect of booster one dose of hepatitis B vaccine after 21-32 years of primary immunization in Zhengding Country of Hebei Province. Methods: A total of 322 participants who were born between 1986 and 1996, received a full course of primary vaccination with plasma-derived hepatitis B vaccine (HepB), had no experience with booster vaccination, were HBsAg, anti-HBcnegative, had anti-HBs<10 mIU/ml, completed the booster and had laboratory results were enrolled between August 2017 to February 2018. A simple random method was uesd to randomly assigned 322 subjects to two groups, receiving a booster dose of HepB derived from either Saccharomyces cerevisiae ï¼»HepB (SC), (151 cases)ï¼½ or Chinese hamster ovary-derived HepB ï¼»HepB (CHO), (171 cases)ï¼½, the dose was 20 µg. Blood samples were collected 30 days after boosting and quantitatively tested for the geometric mean concentration (GMC) of anti-HBs to assess immunological effect. The related influencing factors of GMC and seroconversion rates of anti-HBs were analyzed by multiple linear regression and multivariate logistic regression models. Results: The 266 subjects (82.61%) had anti-HBs≥ 10 mIU/ml, and GMC was (131.63±12.94) mIU/ml.The seroconversion rates of anti-HBs in the anti-HBs<2.5 mIU/ml group and 2.5-10 mIU/ml group were 74.54% (161 cases) and 99.06% (105 cases), respectively (P<0.001).The seroconversion rates of anti-HBs after one dose of HepB (CHO) was higher than that of one dose of HepB (SC), the seroconversion rates were 87.13% (149 cases) and 77.48% (117 cases), respectively (P=0.023). Participants boostered with HepB (CHO) was the factor influencing the effect of strengthening immunization compared with boostered with HepB (SC), and OR (95%CI) was 1.91 (1.02-3.56) (P=0.042).Compared with anti-HBs<2.5 mIU/ml, prebooster anti-HBs was between 2.5 mIU/ml and 10 mIU/ml was the related factor of seroconversion rates of anti-HBs after booster immunization, and OR (95%CI) was 36.15 (4.91-266.02) (P<0.001). Conclusion: Participants boostered withone dose of HepB had a good immune response. Pre-booster anti-HBs concentration and a variety of vaccine were related factors of immune response.


Subject(s)
Hepatitis B Vaccines , Hepatitis B/prevention & control , Animals , CHO Cells , Cricetinae , Cricetulus , Follow-Up Studies , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Immunization, Secondary , Vaccination
4.
J Physiol Pharmacol ; 70(2)2019 Apr.
Article in English | MEDLINE | ID: mdl-31443091

ABSTRACT

The proliferation of vascular smooth muscle cells plays a crucial role in pathogenesis of cardiovascular disease. The principal objective of this study was to determine the effects of Ojeoksan (OJS) on human aortic smooth muscle cell (HASMC) proliferation induced by tumor necrosis factor α (TNF-aα). Thymidine incorporation after TNF-α treatment was increased and this effect was inhibited significantly by OJS treatment. HASMC proliferation and migration by kinetic live cell imaging were also reduced by treatment with OJS. TNF-α induced the expression of cyclins/cyclin-dependent kinases (CDKs) and reduced the expression of p21waf1/cip1/p27kip1. However, OJS also attenuated the expression of TNF-α-induced cell-cycle regulatory proteins. The results of Western blot analysis demonstrated that the TNF-α treated HASMC secreted gelatinases, probably including MMP-2/-9, which may be involved in the invasion and migration of HASMC. Additionally, OJS suppressed the mRNA expression levels of matrix metalloproteinase-2/-9 (MMP-2/-9) in a dose-dependent manner. OJS inhibited the production of TNF-α-induced hydrogen peroxide (H2O2) and the formation of DCF-sensitive intracellular reactive oxygen species (ROS). Further, OJS suppressed the nuclear translocation and phosphorylation of inhibitor of kappa B-α (IκB-α) of nuclear factor κB (NF-κB) under TNF-α conditions. Our results demonstrate that OJS exerts inhibitory effects on TNF-α-induced HASMC proliferation and migration, suggesting the involvement of the inhibition of both MMP-2 and MMP-9 expressions, and the downregulation of ROS/NF-κB signaling. Thus, herbal decoction OJS may be a possible therapeutic approach to the inhibition of cardiovascular disease including atherosclerosis.


Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Aorta/drug effects , Aorta/metabolism , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Down-Regulation/drug effects , Humans , Hydrogen Peroxide/pharmacology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , NF-kappa B/metabolism , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolism
5.
Zhonghua Zhong Liu Za Zhi ; 40(10): 793-800, 2018 Oct 23.
Article in Chinese | MEDLINE | ID: mdl-30392346

ABSTRACT

Non-small cell lung cancer (NSCLC) is one of the malignant diseases with high morbidity, high mortality and poor prognosis in China and worldwide, and the progression of which is significantly related to abnormal angiogenesis. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), inhibits angiogenesis during tumor progression. It has been widely demonstrated to improve the survival of NSCLC patients. Therefore, bevacizumab is approved and recommended as the first-line treatment of advanced NSCLC by a number of countries and regions. In this paper, various large-scale clinical trials are analyzed to highlight the current clinical applications of bevacizumab in advanced NSCLC, especially patients with EGFR mutations. In addition, this review focuses on the efficacy, safety and predict factors of bevacizumab as anti-angiogenic therapy, in order to screen the patients who can acquire the maximal benefit.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/blood supply , China , Humans , Lung Neoplasms/blood supply
6.
Ann Oncol ; 28(10): 2443-2450, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28945850

ABSTRACT

BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Crown Ethers/therapeutic use , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Crown Ethers/adverse effects , ErbB Receptors/metabolism , Exons , Female , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Maintenance Chemotherapy , Male , Middle Aged , Mutation , Neoplasm Staging , Pemetrexed/administration & dosage , Pemetrexed/adverse effects , Quinazolines/adverse effects
7.
J Physiol Pharmacol ; 68(2): 215-221, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28614771

ABSTRACT

Mantidis ootheca (Sang Piao Xiao) is well known mantis eggs in a foamy pouch. The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of the aqueous extract of Mantidis ootheca (AMO) in rat aorta and vascular endothelial cells. AMO was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aortic rings. The roles of the nitric oxide (NO) signaling in the AMO-induced effects were tested in human umbilical vein endothelial cells (HUVECs). HUVEC treated with AMO produced higher amount of NO compared to control. However, AMO-induced increases in NO production were blocked by pretreatment with NG-nitro-L-arginine methylester (L-NAME) or wortmannin. AMO increased in phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt in HUVECs, which were attenuated by a NOS and Akt inhibitors. In aortic ring, AMO-induced dose-dependent relaxation of phenylephrine-precontracted aorta was abolished by removal of functional endothelium. Pretreatment with L-NAME, 1H-[1,2,4]-oxadiazolo-[4,3-alpha]-quinoxalin-1-one (ODQ), and KT5823 inhibited the AMO-induced vasorelaxation. Similarly, wortmannin and LY-294002, an inhibitors of the phosphatidylinositol 3-kinase (PI3K), an upstream signaling molecule of eNOS, attenuated the AMO-induced vasorelaxation. Moreover, AMO-induced increases in cGMP production were blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of AMO was attenuated by tetraethylammonium, 4-aminopyridine, and glibenclamide. We conclude that AMO relaxed vascular smooth muscle via endothelium-dependent activation of PI3K/Akt-mediated NO-cGMP-PKG signaling pathway and possible involvement of K+ channel.


Subject(s)
Complex Mixtures/pharmacology , Mantodea , Zygote , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Aorta, Thoracic/physiology , Cell Survival/drug effects , Cells, Cultured , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Male , Nitric Oxide/metabolism , Nitrites/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology
8.
HNO ; 65(11): 910-915, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28567477

ABSTRACT

BACKGROUND: Chronic facial paralysis induces degenerative facial muscle changes on the involved side, thus, making the individual seem as older than their actual age. Furthermore, contralateral facial hypertrophy aggravates facial asymmetry. A thread-lifting procedure has been used widely for correction of a drooping or wrinkled face due to the aging process. In addition, botulinum toxin injection can be used to reduce facial hypertrophy. The aim of study was to evaluate the effectiveness of thread lifting with botulinum toxin injection for chronic facial paralysis. METHODS: A total 34 of patients with chronic facial paralysis were enrolled from March to October 2014. Thread lifting for elevating loose facial muscles on the ipsilateral side and botulinum toxin A for controlling the facial muscle hypertrophy on the contralateral side were conducted. Facial function was evaluated using the Sunnybrook grading system and dynamic facial asymmetry ratios 1 year after treatment. RESULTS: All 34 patients displayed improved facial symmetry and showed improvement in Sunnybrook scores (37.4 vs. 83.3) and dynamic facial asymmetry ratios (0.58 vs 0.92). Of the 34 patients, 28 (82.4%) reported being satisfied with treatment. CONCLUSION: The application of subdermal suspension with a reabsorbable thread in conjunction with botulinum toxin A to optimize facial rejuvenation of the contralateral side constitutes an effective and safe procedure for face lifting and rejuvenation of a drooping face as a result of long-lasting facial paralysis.


Subject(s)
Facial Paralysis , Minimally Invasive Surgical Procedures , Skin Aging , Adult , Aged , Botulinum Toxins, Type A/therapeutic use , Facial Muscles , Facial Paralysis/surgery , Female , Humans , Male , Middle Aged , Neuromuscular Agents/therapeutic use , Young Adult
9.
Article in English | MEDLINE | ID: mdl-28393417

ABSTRACT

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.


Subject(s)
Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Morpholines/therapeutic use , Nausea/prevention & control , Vomiting/prevention & control , Adult , Aged , Aprepitant , Asian People , China , Cisplatin/adverse effects , Dexamethasone/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Granisetron/therapeutic use , Humans , Male , Middle Aged , Nausea/chemically induced , Treatment Outcome , Vomiting/chemically induced , Young Adult
10.
Zhonghua Zhong Liu Za Zhi ; 39(2): 81-85, 2017 Feb 23.
Article in Chinese | MEDLINE | ID: mdl-28219199

ABSTRACT

Lung cancer still remains the leading cause of cancer-related death worldwide. Recent development of molecular targeted therapies, especially the emergence of epidermal growth factor receptor (EGFR) inhibitors, has made an enormous progress for the treatment of non-small cell lung cancer (NSCLC). However, targeted therapy still faces many problems including acquired resistance. Several clinical trials have proved that targeted therapy can significantly improve the progression-free survival (PFS), but there are still many things needed to be improved. Thus, oncologists still have a long way to go for realizing precision medicine. The present article illustrates the impact of precision medicine on the treatment of lung cancer and describes how to improve the treatment level of lung cancer, aiming to give an inspiration to the medical oncologists.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Molecular Targeted Therapy , Precision Medicine , Disease-Free Survival , Humans , Protein Kinase Inhibitors/therapeutic use
11.
Eur Rev Med Pharmacol Sci ; 20(13): 2805-11, 2016 07.
Article in English | MEDLINE | ID: mdl-27424979

ABSTRACT

OBJECTIVE: To establish and develop a reliable and simple Real-time PCR assay with high resolution melting (Real-time PCR-HRM) method for detection epidermal growth factor (EGFR) and BIM mutation of lung cancer and looking for effective targeted drugs to control lung cancer. PATIENTS AND METHODS: A total of 6858 participants (2538 cases with lung cancer and 4275 healthy controls who took part in the study by doing the physical examination in Shanghai Xuhui community) were recruited in the study. Clinical characteristics and 5 ml peripheral blood were collected from each participant, and the DNA has been extracted, which were determined the EGFR and BIM mutation by Real-time PCR-HRM. Data were recorded and Statistical analyses. RESULTS: All samples completed the study. BIM deletion polymorphism was no related with age, sex, and smoking or EGFR mutation. CONCLUSIONS: There were no relations among BIM deletion polymorphism, EGFR mutation or lung cancer risk. HRM is a novel procedure and provides rapid, sensitive, specific and simultaneous detection for gene mutation of cancer patients for predicting the efficacy of targeted therapy.


Subject(s)
Bcl-2-Like Protein 11/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Real-Time Polymerase Chain Reaction , China , Humans , Mutation
12.
PLoS One ; 10(7): e0131278, 2015.
Article in English | MEDLINE | ID: mdl-26147288

ABSTRACT

BACKGROUND: Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC. METHODS: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015). RESULTS: Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06). CONCLUSION: Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Multicenter Studies as Topic/statistics & numerical data , Neoplasm Proteins/antagonists & inhibitors , Paclitaxel/administration & dosage , Pemetrexed/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Publication Bias , Randomized Controlled Trials as Topic/statistics & numerical data , Smoking/epidemiology , Treatment Outcome , Young Adult , Gemcitabine
13.
Lung Cancer ; 80(3): 333-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23510626

ABSTRACT

BACKGROUND: The X-box binding protein 1 (XBP1) is a critical transcription factor in the endoplasmic reticulum stress response, which is essential for the maintenance of cellular homeostasis. Here, we investigated whether the regulatory variant rs2269577 of the XBP1 gene influences clinical outcome in advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. PATIENTS AND METHODS: We recruited 663 Chinese patients with advanced NSCLC treated with platinum-based regimens and assessed the association between rs2269577 and clinical outcome. Subsequent functional analyses, including real-time quantitative PCR and dual-luciferase assays, were performed to explore possible molecular mechanisms. RESULTS: The G/G genotype of rs2269577 was significantly associated with severe gastrointestinal toxicity compared with the homozygous C/C genotype (P=0.012, odds ratio=2.755), particularly in the female, performance status 0-1, and adenocarcinoma subgroups. No significant relevance was found between rs2269577 and treatment efficacy. In gastric epithelial cells, in vitro molecular analyses demonstrated that XBP1 mRNA expression levels decreased after treatment with cisplatin and the G allele of rs2269577 weakened the transcriptional activity of the XBP1 promoter. CONCLUSION: This is the first study to evaluate the effect of XBP1 polymorphism on severe chemotherapy-related adverse outcomes in platinum-treated advanced NSCLC patients using both pharmacogenomics and functional molecular analyses.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , DNA-Binding Proteins/genetics , Gastrointestinal Tract/pathology , Lung Neoplasms/drug therapy , Platinum/administration & dosage , Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , China , Drug-Related Side Effects and Adverse Reactions , Female , Gastrointestinal Tract/drug effects , Genotype , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Polymorphism, Genetic , Promoter Regions, Genetic , Regulatory Factor X Transcription Factors , X-Box Binding Protein 1
14.
Tumour Biol ; 34(2): 953-61, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23412975

ABSTRACT

Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.


Subject(s)
Adenosine Triphosphatases/genetics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Cell Cycle Proteins/genetics , Lung Neoplasms/mortality , Organoplatinum Compounds/adverse effects , Polymorphism, Single Nucleotide/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , DNA/blood , DNA/genetics , Female , Follow-Up Studies , Haplotypes/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Neutropenia/chemically induced , Polymerase Chain Reaction , Prognosis , Survival Rate , Valosin Containing Protein
15.
J Obstet Gynaecol ; 31(7): 586-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21973128

ABSTRACT

Despite barium being used as a contrast media for decades, the specific assessment of its safety in pregnant women is scarce. We are reporting the favourable pregnancy outcome in women who were inadvertently exposed to barium swallow and associated ionising radiation, early in pregnancy. A control group of age- and gravidity-matched unexposed pregnant women was also included. There were 32 live-born babies in the exposed group and 94 in the control group. Women had undergone diagnostic upper gastrointestinal tract (UGT) fluoroscopic examination at 3.3 ± 1.5 weeks' gestation. Estimated maternal radiation dose secondary to barium swallow varied widely, the maximum dose was estimated to be 2.45 mSv. Similar pregnancy outcomes were observed between the groups. The number of babies born with major malformations was not significantly different (p = 1.0) between cases and controls: one (3.1%) vs three (3.2%), respectively. In conclusion, our small prospective cohort study of women suggests no association between inadvertent exposure to ionising radiation and barium sulphate during fluoroscopic barium swallow and adverse fetal outcomes.


Subject(s)
Barium Sulfate/adverse effects , Contrast Media/adverse effects , Gastrointestinal Tract/diagnostic imaging , Gestational Age , Pregnancy Outcome , Abnormalities, Drug-Induced/epidemiology , Adult , Female , Fluoroscopy , Humans , Pregnancy , Pregnancy Trimester, First , Prospective Studies
16.
Ultrasound Obstet Gynecol ; 38(6): 716-21, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21919103

ABSTRACT

OBJECTIVE: To evaluate the ultrasonographic features of adenoma malignum, a minimal deviation adenocarcinoma of the uterine cervix. METHODS: Eighteen consecutive patients with pathologically confirmed adenoma malignum were enrolled in this study at two institutions. Preoperative ultrasound examination was performed and the results were available in 11 patients. We analyzed retrospectively the gray-scale ultrasound findings for the following morphologic characteristics: cervical enlargement, as well as size, location and ultrasonographic characteristics of lesions. In five patients we also evaluated Doppler features with regard to intralesional vascularity. RESULTS: The cervix was enlarged in 73% (8/11) of cases. The mean greatest tumor diameter was 4.2 (range, 2.5-6.8) cm. In five (45%) cases, the cervix was completely infiltrated by the tumor. At gray-scale ultrasound examination, three (27%) tumors were multilocular lesions, four (36%) were multilocular lesions with solid components and four (36%) were solid lesions. In the multilocular lesions with or without a solid component, locules tended to be 1 cm or less in average diameter (86%, 6/7 cases) and there tended to be 11-20 in number (57%, 4/7 cases). In most (57%, 4/7) cases the locular fluid was homogeneously hypoechoic. Most (75%, 3/4) solid lesions manifested heterogeneous echogenicity. The five (100%) tumors examined with Doppler manifested moderate or abundant color content on color or power Doppler. CONCLUSIONS: Adenoma malignum can appear sonographically as solid, multilocular and multilocular solid cervical lesions. Awareness of its clinical and ultrasonographic features might improve diagnosis before surgery.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Ultrasonography, Doppler, Color/methods , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Early Detection of Cancer , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/surgery , Vaginal Discharge/etiology
17.
J Obstet Gynaecol ; 30(6): 559-62, 2010.
Article in English | MEDLINE | ID: mdl-20701501

ABSTRACT

X-ray exposure, especially if directed to the abdominal region, is of major concern for pregnant women and their physicians. In this study, favourable long-term outcomes are reported in a series of babies born to women inadvertently exposed to barium enema, and associated ionising radiation, early in pregnancy. Six singleton babies were vaginally delivered without any evidence of gross malformations. There was one voluntary abortion. Follow-up on five of the babies was performed over the course of at least 4 years. All the children were deemed healthy and had developed milestones according to their age. Our findings support larger studies suggesting barium enema is not a teratogenic agent. Collectively, this research can be used to counsel women undergoing radiological procedures early in pregnancy.


Subject(s)
Barium Sulfate , Pregnancy/radiation effects , Adult , Contrast Media , Enema , Female , Humans , Pregnancy Trimester, First
18.
Phys Med Biol ; 53(17): 4639-49, 2008 Sep 07.
Article in English | MEDLINE | ID: mdl-18695296

ABSTRACT

Navigating an untethered micro device in a living subject is of great interest for both diagnostic and therapeutic applications. Magnetic propulsion of an untethered device carrying a magnetic core in it is one of the promising methods to navigate the device. MRI gradients coils are thought to be suitable for navigating the device since they are capable of magnetic propulsion in any direction while providing magnetic resonance images. For precise navigation of the device, especially in the peripheral region of the gradient coils, the concomitant gradient fields, as well as the linear gradient fields in the main magnetic field direction, should be considered in driving the gradient coils. For simple gradient coil configurations, the Maxwell coil in the z-direction and the Golay coil in the x- and y-directions, we have calculated the magnetic force fields, which are not necessarily the same as the conventional linear gradient fields of MRI. Using the calculated magnetic force fields, we have synthesized gradient waveforms to navigate the device along a desired path.


Subject(s)
Magnetic Resonance Imaging/methods , Algorithms , Artifacts , Computer Simulation , Equipment Design , Magnetics , Models, Statistical , Signal Processing, Computer-Assisted , Software , Time Factors
19.
Article in English | MEDLINE | ID: mdl-18003482

ABSTRACT

In the recent molecular imaging studies of the magnetic resonance imaging field, in-vivo cell tracking is becoming an issue for the observation of cell therapy and disease behavior. In order to perform cell tracking, high resolution images and long-term studies are required, because those images make better performance than low resolution images in the recognition of cells and cells are traced at least two weeks. Image registration is an essential image processing technique for long-term imaging. In this study, we proposed the image registration technique using ferrite-composite micro- beads which could be used as substitutes for the cells labeling MR contrast agent such as superparamagnetic iron oxide (SPIO) nanoparticles. Registration of sheep brain images tagging micro-beads was performed with the sufficient accuracy for cell tracking.


Subject(s)
Brain/cytology , Ferric Compounds , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Microspheres , Animals , Sheep
20.
Article in English | MEDLINE | ID: mdl-18002852

ABSTRACT

RF coils play an important role to acquire MR images with the maintenance of high homogeneity in high field MR system more than 3.0 T. Many kinds of RF coils such as birdcage coil, STR, surface coil, and phase array coil have been used, however, the good uniformity of a coil has always been an issue. In this paper, comparison of B(1) homogeneity between birdcage and phase array coil was investigated using FDTD method at 3.0 T MRI in order to develop RF coils with the high uniformity. Three different configurations of the FDTD simulation were performed like as using a free space configuration, water phantom configuration, and head mesh model. B1 homogeneity was calculated to the case of birdcage coil and 8-channel phase array coil in each configuration of simulation. Improvement on the homogeneity of the images and reduction of standing wave effect was achieved with comparing the real MR images with the result from simulation.


Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging , Radiography
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