Li Zhang

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (87)138.92 Total impact

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    ABSTRACT: To determine the prognostic significance of the detection of the minimal residual disease (MRD) in children with AML1/ETO AML, we compared the results of reverse-transcription polymerase chain reaction (RT-PCR) and quantitative reverse-transcription polymerase chain reaction (RQ-PCR).
    Pediatric Blood & Cancer 06/2014; · 2.35 Impact Factor
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    ABSTRACT: To determine the expression level of silent mating-type information regulation 2 homologue 1 (SIRT1) in bone marrow biopsy tissues among children with acute myeloid leukemia (AML) and analyze its relationship with the prognosis of AML patients.
    06/2014; 16(6):614-618.
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    ABSTRACT: To estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).
    Zhonghua er ke za zhi. Chinese journal of pediatrics 06/2014; 52(6):449-54.
  • 05/2014; 35(5):479.
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    ABSTRACT: To evaluate the frequency of the nucleophosmin (NPM1) gene and the CCAAT/enhancer binding protein α gene (CEBPA) through polymerase chain reaction (PCR) array in pediatric patients with cytogenetically normal acute myeloid leukemia (CN-AML) and explore the clinical significances of these mutations.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 04/2014; 52(4):303-307.
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    ABSTRACT: To observe the efficacy of polyethylene glycol conjugated asparaginase (peg-asp) for induction treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL). A total of 268 newly diagnosed children with ALL enrolled in CCLG-2008 from January, 2010 to August, 2012 were analyzed. Patients received either native Escherichia coli asparaginase or pegaspargase along with multiagent chemotherapy during remission induction treatment. Status of bone marrow aspiration was assessed on day 15, day 33 (M1, M2, M3). Of the 268 patients stratified, 37.3% (n = 100) were SR, 32.1% (n = 86) were IR, and 31.6% (n = 82) were HR; 159 patients received native Escherichia coli asparaginase and 109 patients received pegaspargase. Characteristics of two groups in age, sex, blood count at diagnosis, immunophenotype and response to prednisolone had no significant difference (P > 0.05). Bone marrow status on day 15 in pegaspargase group was M1 in 70 (64.2%) cases, M2 in 23 (21.1%) and M3 in 16 (14.7%), while in native Escherichia coli asparaginase group, M1 in 112 (70.4%) cases, M2 in 21 (13.2%) and M3 in 26 (16.4%), respectively (χ(2) = 2.938, P = 0.230). Bone marrow status on day 33 was M1 in 105 (96.3%), M2 in 3 (2.8%) and M3 in 1 (0.9%) in pegaspargase group, while it was M1 in 154 (96.9%) cases, M2 in 5 (3.1%) and M3 in native Escherichia coli asparaginase group, respectively (χ(2) = 1.494, P = 0.474). Domestic pegaspargase of our country can achieve the similar efficacy in induction treatment for ALL patients as compared with native Escherichia coli asparaginase. The drug could be considered as not only the choice for allergic patients but also a first-line alternative for new patients.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 03/2014; 52(3):215-7.
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    ABSTRACT: Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development.
    Nature Genetics 02/2014; · 35.21 Impact Factor
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    ABSTRACT: Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.
    Cancer Chemotherapy and Pharmacology 02/2014; · 2.80 Impact Factor
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    ABSTRACT: To compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF). The authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on. (1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival. The use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.
    Zhonghua er ke za zhi. Chinese journal of pediatrics 02/2014; 52(2):84-9.
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    ABSTRACT: Extensive studies of the genetic aberrations related to human diseases conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. Over the time, a series of cutting-edge high-throughput genetic tests, such as microarrays and next-generation sequencing, have been developed and incorporated into routine clinical practice. Although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. In this article, we have summarized the recent advances in FISH application for both de novo discovery and routine detection of chromosomal rearrangements, amplifications, and deletions that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. In addition, we have reviewed the recent developments in FISH methodology as well.
    Biomarker research. 01/2014; 2(1):3.
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    ABSTRACT: Sokal, Euro and newly developed EUTOS scoring systems were validated in 220 Chinese chronic phase chronic myeloid leukemia (CP-CML) patients treated with frontline imatinib. In the EUTOS low-risk and high-risk groups, the 5-year OS was 98.7% vs 71.4% (P < 0.0001), and the 5-year cumulative incidence of complete cytogenetic response (CCyR) was 92.4% vs 53.8% (P < 0.0001). EUTOS score also predicted progression-free survival and duration of CCyR. Low EUTOS index predicted for CCyR. However, Sokal and Euro scores mainly couldn’t discriminate the intermediate-risk from high-risk group in either survival or CCyR. EUTOS score forecasts the prognosis of CP-CML patients treated with first-line imatinib.
    Leukemia Research. 01/2014;
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    ABSTRACT: The efficacy of pemetrexed in the second-line treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) has been shown to be similar to that of docetaxel in a recent study; additionally, pemetrexed was associated with much better safety and toxicity profiles. Here, the survival without common toxicity criteria grade 3/4 toxicity (SWT) data from a post hoc analysis of this recent prospective NSCLC study in Chinese patients is reported. This post hoc analysis differs from the main study; it focuses on the nonsquamous population to align with the current approval for pemetrexed in China. A total of 154 patients with nonsquamous NSCLC received either pemetrexed (500 mg/m(2) intravenously (IV)) or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. SWT was analyzed using Kaplan-Meier and univariate Cox methods. Patients treated with pemetrexed had a longer median SWT than patients treated with docetaxel (7.4 months versus 1.2 months; unadjusted hazard ratio = 0.59, 95% confidence interval (CI): 0.41-0.84; P = 0.003). At 12 and 18 months, the SWT event-free probability for pemetrexed patients (18 months: 24.5%, 95%CI 13.9%-36.6%, vs. 12.3%, 95% CI 4.8%-23.6%) was greater than that for docexatel patients (12 months: 37.3%, 95% CI 26.5%-48.0%, vs. 23.3%, 95% CI 14.4-33.4). The progression-free survival without common toxicity criteria grade 3/4 toxicity (PFS-WT) was also statistically significantly longer for patients treated with pemetrexed than patients treated with docetaxel (1.9 months vs. 1.1 months, P = 0.002). Chinese patients with nonsquamous NSCLC disease treated with pemetrexed had improved SWT beyond 6 months than those receiving docetaxel. This analysis supports a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of Chinese nonsquamous NSCLC patients.
    Chinese medical journal 12/2013; 126(24):4624-8. · 0.90 Impact Factor
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    ABSTRACT: Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P<0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. The median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). The response rate among six regimens was significantly different (P=0.017); There was not statistical significance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. The differences of OS and PFS between six regimens in second-line therapy were not statistically different (P=0.914, P=0.293). The most significant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. The most optimal second-line chemotherapy regimen with definite curatice effect was controversial.
    Zhongguo fei ai za zhi = Chinese journal of lung cancer 11/2013; 16(11):572-578.
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    ABSTRACT: At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients. Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant. 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P<0.05). The maximum diameter of tumor had a significant influence on PFS only in univariate analysis. For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no benefit on them.
    Zhongguo fei ai za zhi = Chinese journal of lung cancer 11/2013; 16(11):596-602.
  • Zhonghua bing li xue za zhi Chinese journal of pathology 11/2013; 42(11):726-8.
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    ABSTRACT: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
    The Lancet Oncology 08/2013; · 25.12 Impact Factor
  • Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 05/2013; 34(5):449-452.
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    ABSTRACT: Cancer is the second leading cause of death around the world. Cancer may be induced by viral infection (EBV, HBV and HPV), bacterial infection (Helicobacter pylori), carcinogen, ultraviolet (UV) radiation exposure, and genetic mutation. Tumor can be suppressed by traditional surgery, radiotherapy, and/or chemotherapy with devastating side effects and very poor quality of postoperative life. The therapeutic index has been further promoted by the newly developed nanomedicine. However, the disseminated tumor cells can result in micrometastases. So the cancer can just be supresssed but not cured by these ways. Fortunately, the developments of immunology have successfully improved many disciplines with special effort on oncology. Various immune cells including B cells, T-lymphocytes (TL), natural killer (NK) cells, dendritic cells (DCs), macrophages, and polymorphonuclear leukocytes are recruited to the tumor. These immune cells can recognize, eliminate, and protect the body from viral, bacterial infections, and the transformed cells (pre-cancer cell) extension. The modification of host immune system, and/or the utilization of components of the immune system for cancer treatment are called immunotherapy. The immunotherapy is not only to target and kill tumor cells in a specific manner, but also to alert the immune system to eradicate the disseminated tumor cells present in the blood circulation and micro-metastases in remote organs. Herein, the development of immunology, cancer immunotherapy, tumor immunoescape was introduced firstly. Then the correlations between host, the tumor and the nano particulates were proposed. And how to improve the cancer immunotherapy by finely nanocarrier's engineering (nanoimmunotherapy) was systematically illustrated with special focus on the unique pathology of tumor microenviroments and properties of immuno cells.
    Mini Reviews in Medicinal Chemistry 03/2013; · 2.87 Impact Factor
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    ABSTRACT: CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR=1.23, 95% CI=0.99-1.53, P=0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR=1.76, 95% CI=1.32-2.33, P<0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI=1.15-1.57, P<0.001). This effect was even more pronounced in smokers (OR=2.98, 95% CI=1.69-5.26, P<0.001), demonstrating that gene-smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers.
    European journal of cancer (Oxford, England: 1990) 02/2013; · 4.12 Impact Factor

Publication Stats

167 Citations
138.92 Total Impact Points

Institutions

  • 2002–2014
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2013
    • Tongji Hospital
      Wu-han-shih, Hubei, China
  • 2012–2013
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
    • Beijing University of Chemical Technology
      Peping, Beijing, China
    • Sun Yat-Sen University Cancer Center
      Shengcheng, Guangdong, China
  • 2011–2012
    • China Academy of Chinese Medical Sciences
      Peping, Beijing, China
  • 2009
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China