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author:("Guo, liming")
1.  Pemetrexed versus vinorelbine treatment of advanced non-squamous non-small cell lung cancer in elderly patients 
Molecular and Clinical Oncology  2013;1(3):553-557.
Pemetrexed, a multitargeted antifolate agent, has been shown to have clear activity in non-squamous non-small cell lung cancer (NSCLC). The aim of this retrospective studywas to evaluated the efficacy and toxicity of pemetrexed vs. vinorelbine in NSCLC elderly patients. Chemotherapy-naive patients aged ≥70 years with stage IIIB/IV non-squamous NSCLC and performance status ≤2 were eligible for inclusion in this study. Patients were selected to receive pemetrexed 500 mg/m2 (day 1) or vinorelbine 25 mg/m2 (days 1 and 8) every 21 days. In total, 62 patients were enrolled in the present study. Thirty-six patients were treated with pemetrexed, and 26 with vinorelbine. The median number of cycles received was six in the pemetrexed group vs. four in the vinorelbine group. Pemetrexed demonstrated a significantly higher disease control rate (DCR) (80.5 vs. 65.3%; P=0.011), and an improvement in progression-free survival (6.5 vs. 4.0 months; P=0.018) compared to vinorelbine. Neutropenia occurred in more patients in the vinorelbine group compared to the pemetrexed group, grade 3–4 neutropenia was observed in 53.8 and 11.1% of patients in the two groups, respectively (P<0.001). Pemetrexed-treated patients experienced lower frequencies of anemia, thrombocytopenia and non-hematologic toxicities compared to vinorelbine-treated patients. The toxicity profiles for the two treatment groups were mild and tolerable. In conclusion, pemetrexed improved DCR, progression-free survival, and presented a lower incidence of treatment-related adverse events compared to vinorelbine, although overall survival was not significantly improved. As a result, pemetrexed monotherapy might be considered as a good option in the treatment of elderly patients with advanced non-squamous NSCLC.
PMCID: PMC3915481  PMID: 24649210
pemetrexed; vinorelbine; first-line therapy; elderly; lung cancer
2.  Structural basis of LaDR5, a novel agonistic anti-death receptor 5 (DR5) monoclonal antibody, to inhibit DR5/TRAIL complex formation 
BMC Immunology  2012;13:40.
As a member of the TNF superfamily, TRAIL could induce human tumor cell apoptosis through its cognate death receptors DR4 or DR5, which can induce formation of the death inducing signaling complex (DISC) and activation of the membrane proximal caspases (caspase-8 or caspase-10) and mitochondrial pathway. Some monoclonal antibodies against DR4 or DR5 have been reported to have anti-tumor activity.
In this study, we reported a novel mouse anti-human DR5 monoclonal antibody, named as LaDR5, which could compete with TRAIL to bind DR5 and induce the apoptosis of Jurkat cells in the absence of second cross-linking in vitro. Using computer-guided molecular modeling method, the 3-D structure of LaDR5 Fv fragment was constructed. According to the crystal structure of DR5, the 3-D complex structure of DR5 and LaDR5 was modeled using molecular docking method. Based on distance geometry method and intermolecular hydrogen bonding analysis, the key functional domain in DR5 was predicted and the DR5 mutants were designed. And then, three mutants of DR5 was expressed in prokaryotic system and purified by affinity chromatograph to determine the epitope of DR5 identified by LaDR5, which was consistent with the theoretical results of computer-aided analysis.
Our results demonstrated the specific epitope located in DR5 that plays a crucial role in antibody binding and even antineoplastic bioactivity. Meanwhile, revealed structural features of DR5 may be important to design or screen novel drugs agonist DR5.
PMCID: PMC3436762  PMID: 22788777
TRAIL; Death receptor 5; Monoclonal antibody; Apoptosis; Breast cancer
3.  In vivo99mTc-HYNIC-annexin V imaging of early tumor apoptosis in mice after single dose irradiation 
Apoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. 99mTc-HYNIC-annexinV has been reported as a promising agent for in vivo apoptosis imaging. The purpose of this study is to evaluate the feasibility of in vivo99mTc-HYNIC-annexinV imaging of radiation- induced apoptosis, and to investigate its correlation with radiosensitivity.
Ten days after inoculation of tumor cells in the right upper limbs, the mice were randomly divided into two groups. The imaging group (4 mice each level, 4 dose levels) was injected with 4-8 MBq 99mTc-HYNIC-annexinV 24 hours after irradiation and imaged 1 hr post-injection, and the mice were sacrificed immediately after imaging for biodistribution analysis of annexin V. The observation group (4 mice each level, 2 dose levels) was only observed for tumor regression post-radiation. The number of apoptotic cells in a tumor was estimated with TUNEL assay.
The 99mTc-HYNIC-annexin V uptake in E14 lymphoma significantly increased as the radiation dose escalated from 0 to 8 Gy, and significantly correlated with the number of TUNEL-positive cells (r = 0.892, P < 0.001). The Annexin-V uptake and the number of TUNEL-positive cells in El4 lymphoma were significantly greater than those in S180 sarcoma. With 8 Gy, S180 sarcoma tumor showed scanty apoptosis and less shrinkage while El4 lymphoma showed remarkable apoptosis and complete remission.
99mTc-HYNIC-annexinV in vivo imaging is a feasible method to detect early radiation-induced apoptosis in different tumors, and might be predictive for radiation sensitivity.
PMCID: PMC2768695  PMID: 19814783

Results 1-3 (3)