Aberrant p16 promoter hypermethylation in bronchial mucosae as a biomarker for the early detection of lung cancer.
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Biomedical subjects
Publications and source records attributed to Long-yun Li.
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OBJECTIVE: The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime. METHODS: In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial. RESULTS: In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia. CONCLUSION: Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.
OBJECTIVE: To establish a sensitive and specific HPLC method for the quality control of Rhizoma Coptidis collected from shizhu in chongqing. METHODS: The HPLC fingerprints of Rhizoma Coptidis from shizhu were obtained from Waters instrument. The methods was performed on a Diamonsil C18 column gradient eluted with acetonitrile-0.05 mol/L KH2PO4 (pH3 with H3PO4) at the flow rate of 0.8 m/min. The temperature of column was 25 degrees C and the UV detection wavelength was 270nm. RESULTS: The HPLC fingerprint of Rhizoma Coptis, showing 16 characteristic peaks, was established from 10 lots of Rhizoma Coptis. By comparision of the retention time and the on-line UV spectra of chemical standards, peak 11, 12, 13, 14 and 15 were identified as Epiberberine, Jatrorrhizine, Coptisine, Palmatine and Berberine. CONCLUSION: The HPLC fingerprint of Rhizoma Coptidis with high specificity can be used to control its quality.
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OBJECTIVE: To investigate the antitumor effects and toxicity of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor gefitinib (Iressa) in advanced non-small cell lung cancer (NSCLC). METHODS: The clinical data and quality of life of 66 patients with NSCLC treated with Iressa orally at the dose of 250 mg/d were reviewed, and the data were analyzed by using logistic analysis, chi(2) test and t test. The impact of treatment on disease-related symptoms and quality of life was evaluated with Chinese version of European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30) and QLQ-LC13. RESULTS: Tumor response rate was 33%. Disease control rate, which included both tumor responses and stable disease, was 70%. The mean scores of each functioning scales and global quality of life in QLQ-C30 increased significantly. Response rates were 91% - 100%. Mean scores of disease-related symptoms decreased significantly. Response rates were 73% - 100%. Quality of life and symptom response were correlated with objective tumour response. The 250 mg/day dose of Iressa was well tolerated by patients. The majority of adverse events were grade I or grade II skin rash and diarrhea, which were manageable and reversible. CONCLUSION: Iressa offers a new treatment option providing meaningful tumor control and symptom relief for many patients with advanced NSCLC.
OBJECTIVE: To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (FDG-PET) in lung cancer. METHODS: From September 1999 to April 2003, patients with lung cancer or indeterminate lung lesions on chest CT scan were enrolled, and underwent FDG-PET scanning. RESULTS: Of 104 patients, 64 (60%) had malignancy and 40 (40%) had a benign process. The standard uptake ratio (SUV) in patients with lung cancer was significantly higher than that in patients with benign disease, 4.5 (1.2 - 11.7) and 1.0 (0 - 7.7) respectively. The SUV was not related with histologic type, differentiation, staging and the size of lesion. The diagnostic sensitivity, specificity and accuracy of PET imaging for lung cancer were 88%, 85% and 87% respectively, and the diagnostic specificity and accuracy for lung cancer with PET were significant higher than those with CT scan. The specificity and accuracy of lung lesions with a diameter >or= 1.5 cm with SUV method was better than that of lesions with a diameter < 1.5 cm. In 6 false positive patients, 4 were tuberculosis, 1 fungal infection and 1 organic pneumonia. Both PET and CT scan were poorly sensitive and specific for detecting local lymph node metastasis. CONCLUSIONS: PET had advantages in evaluation of lung lesions, and integrated PET and CT were recommended for detecting local lymph node metastasis.
OBJECTIVE: To investigate the clinical features and diagnostic procedures for diffuse panbronchiolitis in Chinese patients. METHODS: With literature review, the clinical features and diagnostic procedures of diffusely panbronchiolitis in a series of 9 patients with histopathological confirmation were retrospectively described and discussed. RESULTS: Of the 9 cases, 8 had persistent cough, sputum production and exertion dyspnea, 7 had chronic sinusitis, 9 had centrilobular micronodules on chest CT, 7 had coarse crackles, 4 had FEV(1)/FVC < 70%, 5 had PaO(2) < 80 mm Hg and 1 had titer of cold hemagglutinin > or = 1:64. According to the Japanese revised clinical diagnostic criteria for diffuse panbronchiolitis, definite diagnosis could be made in 4 cases, probable in 3 and excluded in 2 cases, respectively, but it was clinically diagnosed or suspected only in 2 cases before clinicopathological confirmation, the remaining 7 cases were missed or mistaken for other diseases. Of the 9 cases, 8 had received transbronchial biopsy and all showed non-specific inflammation, which was in agreement with but nondiagnostic for diffuse panbronchiolitis. CONCLUSIONS: Most cases of diffuse panbronchiolitis can be clinically diagnosed or suggested according to the clinical diagnostic criteria, proposed solely by Japanese experts which should be further validated in non-Japanese populations. If difficulty in diagnosis arises, the diagnosis of diffuse panbronchiolitis should be based on its clinicopathological features and exclusion of other mimicking diseases. Of note, few cases can be confirmed by transbronchial biopsy, and in this case, surgical lung biopsy should be considered.
OBJECTIVE: To analyze the clinical characteristics and treatment of hematogenous disseminated tuberculosis. METHODS: Twenty-seven cases of hematogenous disseminated tuberculosis diagnosed by autopsy from 1961 to 2000 were retrospectively analyzed. RESULTS: Among these patients the disease was acute in 22 cases (including 3 non-reactive) and chronic in 5. Twenty cases (74%) were misdiagnosed before death, most of which were due to concomitant with or misdiagnosed as connective tissue disease, hematological disease or tumor. 63% of the cases had long-term use of corticosteroids or repeated chemotherapy. Most cases showed atypical clinical manifestations and chest X-ray lesions. The positive rate of tuberculin skin test and sputum for smear were low. Autopsy showed that all cases had active lung tuberculosis and the major extra-pulmonary organs involved were liver, spleen and lymph nodes. CONCLUSION: Unaware of the risk for tuberculosis among immune compromised patients was the main reason for misdiagnosis and corticosteroid abuse was common. Physician should be alert to the occurrence of hematogenous disseminated tuberculosis, especially in immune compromised patients with long-term fever and systemic injury. Direct smear and cultural examination as well as newer diagnostic approaches with sputum and tissue may be useful for a rapid and correct diagnosis.
OBJECTIVE: To evaluate the efficacy and safety of Arbidol in the treatment of naturally acquired influenza. METHODS: A randomized, double-blinded, placebo controlled trial was conducted. Subjects were enrolled. The inclusion criteria included: aged 18 to 65 years, presented within 36 hours of onset of influenza symptoms; and had documented temperature of 37.8 degrees C or higher during an influenza outbreak in the community. Individuals were randomly divided Arbidol group (200 mg three times daily for 5 days) or placebo group. RESULTS: Totally 232 individuals were recruited and received medication and follow-up. All of them were qualified to be analyzed for safety as intent-to-treat population (ITT) (113 Arbidol, 109 placebo). Twenty-two (9.48%) were during follow-up or refused to continue the trial, and 210 completed as schecule and identified as PP population (102 Arbidol, 108 placebo). Totally 125 individuals were identified as influenza-infected through laboratory test, which was defined as PPi population (59 Arbidol, 66 placebo). In PPi population, the cumulative alleviation proportion of Arbidol group was significantly higher than that of placebo group. The median duration of illness was 72.0 hours (95% confident interval (CI) 66.00-78.00 hours) in Arbidol group and 96.0 hours (95% CI 87.46-104.54 hours) in placebo group. The median area under the curve (AUC) of decreased total score were significantly higher in Arbidol group than in placebo group, which were 780.00 and 684.00 score-hours respectively. For PP population, similar results were seen. Adverse events reported were similar in Arbidol group and in placebo group. The main adverse events were gastrointestial symptoms and increased transaminase. CONCLUSION: Arbidol was effective and well tolerated in the treatment of early naturally acquired influenza.
Micrometastasis may occur in the early stage of lung cancer and dissemination of lung cancer cells into blood circulation is pivotal for metastasis. Many approaches, such as polymerase chain reaction, magnetic activated cell sorting, flow cytometery, and rare event imaging system, have been developed rapidly. The detection of circulating tumor cells may renew the clinical stage and treatment of lung cancer.
We described 3 cases of advanced bronchioloalveolar carcinoma (BAC), in whom once-daily treatment with 250 mg Gefitinib (Iressa) demonstrated remarkable antitumor effects. Gefitinib may produce dramatic clinical responses when administered to patients with poor performance status who had received heavy platinum/docetaxel-based prior chemotherapy.
OBJECTIVES: To probe Rb2/p130 and p53 gene mutations at their hot-spots by denaturing high-performance liquid chromatography (DHPLC) analysis in sputum samples from lung cancer patients and to evaluate the feasibility of these gene markers in the clinical diagnosis of lung cancer. METHODS: Genomic DNAs were extracted from 47 sputum samples (35 of lung cancer, 12 of benign lung disease) and their parallel peripheral blood lymphoid cells. The genomic DNAs were subjected to PCR amplification of Rb2/p130 gene at exon 19 - 22 and p53 gene at exon 5 - 9. The mutations of Rb2/p130 and p53 were detected by DHPLC by analysis of the PCR products. RESULTS: Of the 47 sputum samples, the Rb2/p130 gene mutation detection rates were 22.86% (8/35) in the lung cancer group and 0 (0/12) in the control group (P = 0.049). The sensitivity and specificity were 22.86% and 100% respectively by using Rb2/p130 gene mutation detection as a diagnostic marker for lung cancer. p53 gene mutation detection rates were 28.57% (10/35) in the lung cancer group and 0 (0/12) in the control group (P = 0.046). The sensitivity and specificity were 28.57% and 100% respectively by using p53 gene mutation detection as a diagnostic marker for lung cancer. The sensitivity and specificity reached 51.43% and 100% respectively when Rb2/p130 and p53 gene mutations were combined as diagnostic markers for lung cancer. CONCLUSIONS: Because of the low sensitivity, Rb2/p130 or p53 gene mutation detection alone is not feasible as a gene marker in the clinical diagnosis of lung cancer. The increased sensitivity, by combining the two gene markers, suggests that it may be feasible to use a panel of molecular markers such as p53, Rb2/p130, and others as diagnostic markers for lung cancer.
BACKGROUND: Diffuse panbronchiolitis (DPB) was originally and is still primarily reported in Japan, rarely in other countries. As macrolide therapy is effective for this disease with once dismal prognosis, familiarity with its clinical features is urgently needed, especially for clinicians outside Japan. The objectives of this study were to investigate the clinical features of DPB in a Chinese population and propose diagnostic procedures that will lead to increased awareness of this treatable disease among clinicians, ultimately allowing for more rapid diagnosis. METHODS: After a literature review, the clinical features of DPB were histopathologically confirmed in a series of 9 cases either by open lung biopsy or video-assisted thoracic surgical biopsy, resulting in the largest series of confirmed DPB cases in a non-Japanese population. Here, the cases are retrospectively described and diagnostic procedures are discussed. RESULTS: Persistent cough, sputum, and exertion dyspnea occurred in 89% of patients, a history of or current chronic sinusitis in 78%, centrilobular micronodules appearing on chest CT scans in 100%, coarse crackles in 78%, FEV1/FVC < 70% in 44%, PaO2 < 80 mmHg in 56%, and titer of cold hemagglutinin > or = 1:64 in 11%. According to its clinical diagnostic criteria, diagnosis was definitive in 44%, suggested in 33%, and excluded in 23% at the time of diagnosis. However, DPB was clinically considered before confirmation in only 22% of patients, with the remaining 78% of cases missed or mistaken for other diseases. Of the 9 cases, 8 received transbronchial biopsies before confirmation of the diagnosis, but all showed non-specific inflammation. CONCLUSIONS: Although its clinical features may vary with disease course and ethnic populations, most cases of DPB can be diagnosed or suggested according to clinical diagnostic criteria. However, underdiagnosis as a result of unfamiliarity with its clinical features and diagnostic criteria prevails. If difficulty in diagnosis arises, the diagnosis should be based on clinicopathological features and the exclusion of other diseases. Few cases can be confirmed by transbronchial biopsies; in these cases, either an open-lung biopsy or a video-assisted thoracic surgical lung biopsy should be recommended.
BACKGROUND: Recent studies suggest that circulating DNA may be a potential tumor marker for lung cancer, but most of these studies are conducted between healthy controls and lung cancer patients, with few or no benign lung disease patients included. The objective of this study was to evaluate the performance of plasma DNA quantification in discriminating lung cancer from the healthy and benign lung disease. METHODS: Plasma DNA was extracted with a QIAamp DNA Blood Midi kit and quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36 benign lung disease patients and 67 lung cancer patients. Discrimination power was evaluated by the receiver operating characteristic curve. RESULTS: Plasma DNA values were significantly increased in lung cancer patients, especially in those with metastases, and in benign lung disease patients compared with that in the healthy individuals (P < 0.001, respectively). The values in lung cancer patients were significantly increased compared with that in the benign lung disease patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83) for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for lung cancer versus the healthy and benign lung disease. CONCLUSIONS: Plasma DNA quantification has a strong power to discriminate lung cancer from the healthy and from the healthy and benign lung disease, less power to discriminate lung cancer from benign lung disease. Plasma DNA quantification may be useful as a screening tool for lung cancer.
OBJECTIVE: To provide some new evidences for the identification of medicinal materials of Curcuma. METHOD: Microscopic observation was made to characterize the rhizomes of Curcuma. RESULT AND CONCLUSION: There were no obvious histological and morphological differences among the rhizomes of Curcuma. The distribution of oil cells and vascular bundles as well as the number and diameter of xylem vessels were considered to be the distinguishing features of their rhizomes.
OBJECTIVE: To provide some new evidences for the classfication and identification of medicinal plants of Curcuma. METHOD: A numerical taxonomy by means of cluster analysis and principal Component analysis is used. Combined with RAPD analysis, computer image analysis and chemical analysis, the taxonomical relationships of the plants of Curcuma in China were characterized qualitatively and quantitatively. RESULT AND CONCLUSION: The plants of Curcuma is systematized into 9 species, 1 species complex, 3 cultivated varieties. A lot of taxonomic confusion and disputations were consequently expounded.