Publications by authors named "Xi-Cheng Wang"

45 Publications

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Lancet 2021 07 7;398(10297):303-313. Epub 2021 Jun 7.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.

Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.

Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.

Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.

Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
July 2021

Palliative Gastrectomy versus Gastrojejunostomy for advanced Gastric cancer with outlet obstruction: a propensity score matching analysis.

BMC Cancer 2021 Feb 23;21(1):188. Epub 2021 Feb 23.

Department of Gastric Surgery, Sun Yat-sen University Cancer Center, No.651 Dongfeng Road East, Guangzhou, 510060, Guangdong, China.

Background: Gastric outlet obstruction (GOO) is a late complication of advanced gastric cancer, and it is controversial how to select the therapeutic strategies: gastrojejunostomy and palliative gastrectomy? Therefore, this study was to compare the surgical and survival outcomes of gastrojejunostomy and palliative gastrectomy.

Methods: In total, 199 gastric cancer patients with outlet obstruction treated by surgery between January 2000 and December 2015 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Patients were divided into gastrojejunostomy group and palliative gastrectomy group. Propensity score matching (PSM) was performed to balance the selection bias.

Results: After 1:1 PSM, a total of 104 patients were included for final analysis. The median overall survival (OS) times in the gastrojejunostomy group and palliative gastrectomy group were 8.50 and 11.87 months, respectively (P = 0.243). The postoperative complication rates in the gastrojejunostomy group and palliative gastrectomy group were 19.23% (10/52) and 17.31% (9/52), respectively (P = 0.800), and no treatment-related death was observed. Multivariate analysis showed that periton0eal seeding (P = 0.014) and chemotherapy (P < 0.001) were independent prognostic factors. Among them, peritoneal seeding was a risk factor and postoperative chemotherapy was a protective factor.

Conclusions: Our results indicated that although the surgical complications of palliative gastrectomy were manageable, it showed no survival benefit. Therefore, relieving obstruction symptom, improving patients' quality of life and creating better conditions for chemotherapy appear to be the main therapeutic strategies for advanced gastric cancer with GOO.
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http://dx.doi.org/10.1186/s12885-021-07904-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903659PMC
February 2021

Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19.

Signal Transduct Target Ther 2020 12 24;5(1):294. Epub 2020 Dec 24.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
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http://dx.doi.org/10.1038/s41392-020-00457-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758413PMC
December 2020

Newly synthesized phenanthroimidazole derivatives L082 as a safe anti-tumor and anti-injury inflammation bifunctional compound.

Eur J Pharmacol 2020 Dec 6;889:173571. Epub 2020 Oct 6.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address:

Chemotherapy drugs exerts beneficial antitumor activity before and after cancer surgery. Post-injury complications are a potential hazard after surgical tumor resection. Inflammation caused by surgical stress is known to promote the progression of post-injury complications. Recent studies have found that chemotherapy drugs can promote post-injury inflammatory response, leading to increased post-injury complications. Imidazole derivatives have effective anticancer activity. However, the impact of post-operative inflammation caused by imidazole derivatives is unclear. In this study, two novel phenanthroimidazole derivatives (L082 and L142) were synthesized and characterized. These compounds showed significant inhibitory effects on different tumor cells. The compound L082 also inhibited liver cancer in vivo. In addition, L082 played a significant role in inhibiting the accumulation of inflammatory cells and promoting the elimination of inflammatory cells at the incision, which may be related to inhibiting the production of ROS and NO in oxidative and nitric stress. These results suggest that L082 can be used as a bifunctional drug to suppress tumors and reduce post-injury inflammation complications.
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http://dx.doi.org/10.1016/j.ejphar.2020.173571DOI Listing
December 2020

Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients.

Cell Mol Immunol 2020 05 17;17(5):541-543. Epub 2020 Mar 17.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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http://dx.doi.org/10.1038/s41423-020-0401-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091621PMC
May 2020

Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial.

J Cancer 2019 2;10(14):3214-3223. Epub 2019 Jun 2.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou 510060, China.

: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. : Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. : A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. : Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.
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http://dx.doi.org/10.7150/jca.30123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603389PMC
June 2019

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

N Engl J Med 2019 09 31;381(12):1124-1135. Epub 2019 May 31.

From the Departments of Radiation Oncology (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), Medical Oncology (Y.-H.L.), and Nasopharyngeal Carcinoma (H.-Y.M.) and the Clinical Trials Center (Y.G.), Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), and the Department of Radiation Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University (X.-C.W., Q.-F.S.), Guangzhou, the Cancer Center, Tongji Hospital Affiliated to Tongji Medical College (G.-Q.H., G.-X.L.), and the Cancer Center, Union Hospital, Tongji Medical College (K.-Y.Y., J.H.), Huazhong University of Science and Technology, Wuhan, the Department of Radiation Oncology, First People's Hospital of Foshan, Foshan (N.Z., S.-Q.L.), the Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning (X.-D.Z., L.L.), the Department of Head and Neck Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang (F.J., J.-H.L.), the Department of Radiation Oncology, XiJing Hospital of Fourth Military Medical University, Xi'an (M.S., J.Z.), the Cancer Center (Z.-B.C.), and the Department of Head and Neck Oncology (S.-Y.W., Q.-D.L.), Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, the Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou (Y.T., L.Z.), the Department of Radiation Oncology, Peking University Cancer Hospital, Beijing (Yan Sun, B.-M.Z.), and the Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang (J.-G.L., Y.X.) - all in China; and the Divisions of Radiation Oncology and Medical Sciences, National Cancer Center Singapore, and the Oncology Academic Program, Duke-National University of Singapore Medical School - both in Singapore (M.L.K.C.).

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.

Results: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group.

Conclusions: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).
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http://dx.doi.org/10.1056/NEJMoa1905287DOI Listing
September 2019

Phenanthroimidazole derivatives act as potentinducer of autophagy by activating DNA damage pathway.

Bioorg Chem 2019 07 19;88:102940. Epub 2019 Apr 19.

The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:

A series of imidazo[4,5f][1,10]phenanthroline derivatives (1-6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC of approximately 2.3 ± 0.1 µM, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug.
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http://dx.doi.org/10.1016/j.bioorg.2019.102940DOI Listing
July 2019

Human genome-derived TOP1 matrix attachment region enhances transgene expression in the transfected CHO cells.

Biotechnol Lett 2019 Jul 5;41(6-7):701-709. Epub 2019 Apr 5.

International Joint Research Laboratory for Recombiant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, 453003, Henan, China.

Objectives: To investigate the effect of full-length fragment of DNA topoisomerase I gene (TOP1) matrix attachment regions (MARs) originating from the human genome on transgene expression in Chinese hamster ovary (CHO) cells and explore the underlying mechanisms.

Results: Results showed that TOP1 MAR cannot only enhance the transient and stable transgenic expression of enhanced green fluorescence protein (EGFP) but also increase long-term stability and ratio of positive colonies in transfected CHO cells with TOP1 MAR at the 5' or 3' ends of the EGFP expression cassette. Interestingly, the CHO cells were transfected with the 5',3' TOP1 MAR-containing vector featured the highest transient and stable expression, whereas those with the 3' TOP1 MAR-containing vector exhibited the most effective stability and ratio of positive colonies. We also observed that transgene copy numbers and mRNA of egfp gene were correlated with the expression levels of EGFP protein in polyclonal CHO cells. However, the heterogeneity of expression in monoclonal CHO cells was unaffected by transgene copy number.

Conclusions: The findings may aid in the potential application of TOP1 MAR in expression enhancement of recombinant proteins in mammalian cells.
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http://dx.doi.org/10.1007/s10529-019-02673-7DOI Listing
July 2019

A phenanthroline derivative enhances radiosensitivity of hepatocellular carcinoma cells by inducing mitochondria-dependent apoptosis.

Eur J Pharmacol 2019 Jan 13;843:285-291. Epub 2018 Nov 13.

The First Affiliation Hospital, Guangdong Pharmaceutical University, Guangzhou 510062, China. Electronic address:

Combining radiosensitizers with ionizing radiation (IR) is an effective strategy to increase the radiation therapeutic effect for hepatocellular carcinoma (HCC) patients. A phenanthroline derivative, 2-phenyl-imidazo [4, 5 f] [1, 10] phenanthroline (L02), had been synthesized. This study investigated the radiosensitization and mechanisms of L02 combined with IR against HCC. The radiosensitization of L02 combined with IR was evaluated by the sensitivity enhancement ratio (SER) and the isobolographic analysis. The toxicity of L02 and cisplatin were compared by the zebrafish model. The cell cycle and apoptosis were examined by flow cytometry. DNA damage was measured by comet assay and the expressions of apoptosis related proteins were analyzed by western blotting. L02 was effective in sensitizing HCC to IR. The SERs in HepG2 and BEL7402 were 1.41 and 1.28, respectively. The sensitization of L02 was comparable with cisplatin. L02 treatment with IR had synergistic anti-tumor effect. L02 enhanced the percentage of IR induced apoptosis cells. L02 increased comet tail in comet assay when combined with IR. L02 sensitized HCC to IR by the activation of P53 signaling, the decrease in Bcl-2, up-regulation of cytochrome c and the subsequent activation of caspase-3. L02 sensitizes HCC to IR, mostly likely by inhibiting cell proliferation, inducing DNA damage and mitochondria-dependent apoptosis. L02 may be a novel radiosensitizer for HCC.
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http://dx.doi.org/10.1016/j.ejphar.2018.10.031DOI Listing
January 2019

PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line CNE-2 by inducing endoplasmic reticulum stress, downregulating STAT3 signaling, and modulating the MAPK pathway.

J Cell Physiol 2019 03 7;234(3):2618-2630. Epub 2018 Sep 7.

Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line.
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http://dx.doi.org/10.1002/jcp.27076DOI Listing
March 2019

Dichotomous Roles of Programmed Cell Death 1 on HIV-Specific CXCR5 and CXCR5 CD8 T Cells during Chronic HIV Infection.

Front Immunol 2017 12;8:1786. Epub 2017 Dec 12.

Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.

Background: CXCR5CD8 T cells have been demonstrated to play an important role in the control of chronic viral replication; however, the relationship between CXCR5CD8 T cells, HIV disease progression, and programmed cell death 1 (PD-1) expression profile on CXCR5CD8 T cells during HIV infection remain poorly understood.

Methods: We enrolled a total of 101 HIV patients, including 62 typical progressors, 26 complete responders (CRs), and 13 immune non-responders (INRs). Flow cytometric analysis, immunohistochemical staining, and relative function (i.e., cytokine secretion and PD-1 blockade) assays were performed to analyze the properties of CXCR5CD8 T cells.

Results: HIV-specific CXCR5CD8 T cells in the peripheral blood and distribution of CXCR5CD8 T cells in the lymph node (LN) were negatively correlated with disease progression during chronic HIV infection. PD-1 was highly expressed on CXCR5CD8 T cells and positively associated with peripheral CD4 T cell counts. Functionally, IFN-γ and TNF-α production of CXCR5CD8 T cells were reduced by PD-1 pathway blockade, but the production of IFN-γ and TNF-α from CXCR5CD8 T cells increased in response to TCR stimulation. Interestingly, PD-1 expression was constantly retained on CXCR5CD8 T cells while significantly decreased on CXCR5CD8 T cells after successful antiretroviral treatment in chronic HIV-infected patients.

Conclusion: PD-1CXCR5CD8 T cells are functional cytotoxic T cells during chronic HIV infection. PD-1CXCR5CD8 T cells may represent a novel therapeutic strategy for the disease.
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http://dx.doi.org/10.3389/fimmu.2017.01786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732951PMC
December 2017

Intensity-modulated radiotherapy has superior outcomes to three-dimensional conformal radiotherapy in patients with stage IE-IIE extranodal nasal-type natural killer/T-cell lymphoma.

Oncotarget 2017 Sep 11;8(36):60504-60513. Epub 2017 Mar 11.

Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, People's Republic of China.

We compared the treatment outcomes, toxicities and prognoses of patients with stage IE-IIE extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT). Newly diagnosed early-stage ENKTL patients ( = 173) were enrolled and received extended involved-field radiotherapy following induction chemotherapy. Patients were treated with 3DCRT ( = 98) or IMRT ( = 75). One-to-one matching of the IMRT and 3DCRT groups was performed through propensity score matching, which yielded 23 pairs of patients. The two groups achieved similar complete remission rates before and after radiotherapy ( > 0.05). All patients were followed up for a median of 41 months. The rates of local recurrence-free survival (LRFS, < 0.001), progression-free survival (PFS, = 0.003) and overall survival (OS, = 0.003) were longer in the IMRT than 3DCRT group. In the matched patients, IMRT was still associated with superior LRFS ( = 0.024), but not with improved PFS ( = 0.113) or OS ( = 0.115). Multivariate analysis also suggested IMRT was a favorable independent factor for LRFS (HR = 2.230, = 0.043), but not for PFS ( = 0.195) or OS ( = 0.116). Equivalent acute toxicities were observed for 3DCRT and IMRT; however, among stage II patients who had received cervical irradiation, the rate of late xerostomia was lower in the IMRT than 3DCRT group (38.5% . 66.7%, = 0.046). Overall, IMRT yielded a better treatment response and local control than 3DCRT, and tended to reduce late xerostomia in patients with cervical irradiation, but failed to enhance OS. Thus, IMRT is recommended for the treatment of stage IE-IIE ENKTL patients.
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http://dx.doi.org/10.18632/oncotarget.16138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601157PMC
September 2017

Detection of nasopharyngeal carcinoma susceptibility with single nucleotide polymorphism analysis using next-generation sequencing technology.

Oncotarget 2017 Aug 13;8(32):52708-52723. Epub 2017 Apr 13.

Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with high incidence in South China and East Asia. To provide a theoretical basis for NPC risk screening and early prevention, we conducted a meta-analysis of relevant literature on the association of single nucleotide polymorphisms (SNP)s with NPC susceptibility. Further, expression of 15 candidate SNPs identified in the meta-analysis was evaluated in a cohort of NPC patients and healthy volunteers using next-generation sequencing technology. Among the 15 SNPs detected in the meta-analysis, miR-146a (rs2910164, C>G), HCG9 (rs3869062, A>G), HCG9 (rs16896923, T>C), MMP2 (rs243865, C>T), GABBR1 (rs2076483, T>C), and TP53 (rs1042522, C>G) were associated with decreased susceptibility to NPC, while GSTM1 (+/DEL), IL-10 (rs1800896, A>G), MDM2 (rs2279744, T>G), MDS1-EVI1 (rs6774494, G>A), XPC (rs2228000, C>T), HLA-F (rs3129055, T>C), SPLUNC1 (rs2752903, T>C; and rs750064, A>G), and GABBR1 (rs29232, G>A) were associated with increased susceptibility to NPC. In our case-control study, an association with increased risk for NPC was found for the AG vs AA genotype in HCG9 (rs3869062, A>G). In addition, heterozygous deletion of the GSTM1 allele was associated with increased susceptibility to NPC, while an SNP in GABBR1 (rs29232, G>A) was associated with decreased risk, and might thus have a protective role on NPC carcinogenesis. This work provides the first comprehensive assessment of SNP expression and its relationship to NPC risk. It suggests the need for well-designed, larger confirmatory studies to validate its findings.
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http://dx.doi.org/10.18632/oncotarget.17085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581063PMC
August 2017

Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA.

Molecules 2017 May 20;22(5). Epub 2017 May 20.

Department of Chemistry, Jinan University, Guangzhou 510006, China.

Herein, a series of imidazo[4,5-][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-][1,10] phenanthroline, R = NO₂, ; CF₃, ; Cl, ; OH, ) have been synthesized in yields of 82.3-94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially , exhibited excellent inhibitory activity against the growth of A549 cells with IC of 15.03 μM. Moreover, it's also confirmed that can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that can bind to G-quadruplex DNA, which demonstrated by the increase of melting point of G4 DNA in the presence of , as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the G-quadruplex DNA.
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http://dx.doi.org/10.3390/molecules22050829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154642PMC
May 2017

Radiotherapy improves survival in early stage extranodal natural killer/T cell lymphoma patients receiving asparaginase-based chemotherapy.

Oncotarget 2017 Feb;8(7):11480-11488

Department of Oncology, the First affiliated Hospital of Guangdong Pharmaceutical University, Guangdong 510080, People's Republic of China.

This study retrospectively investigated asparaginase-based chemotherapy treatment outcomes with or without radiotherapy in 143 patients with stage IE-IIE extranodal natural killer/T cell lymphoma (ENKTCL). All patients received a median of three cycles of asparaginase-based chemotherapy, while 121 patients received radiotherapy following the chemotherapy. The complete remission (CR) rate for all patients post-chemotherapy was 58.7%, and rose to 73.4% by the end of treatment. Patients who received radiotherapy achieved better survival outcomes than those who did not (89.7% vs. 49.0% for 2-year overall survival (OS), P<0.001; 86.8% vs. 37.4% for 2-year progression-free survival (PFS), P<0.001). Additionally, even patients who achieved CR post-chemotherapy exhibited differential survival rates with or without radiotherapy (90.8% vs. 60% for 2-year OS, P=0.006; 86.1% vs. 60% for 2-year PFS, P=0.044). Multivariate analysis revealed that radiotherapy was an independent factor favoring OS (HR=0.098, 95%CI=0.031-0.314, P=0.001) and PFS (HR=0.156, 95%CI=0.062-0.396, P=0.001). Thus, radiotherapy is recommended for stage IE-IIE ENKTCL patients treated with asparaginase-based chemotherapy, even in cases of CR following chemotherapy.
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http://dx.doi.org/10.18632/oncotarget.14006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355279PMC
February 2017

Outcomes of Induction Chemotherapy Plus Intensity-Modulated Radiotherapy (IMRT) Versus IMRT Plus Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Study.

Transl Oncol 2016 Aug;9(4):329-35

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Purpose: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma.

Methods: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression.

Results: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse.

Conclusions: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.
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http://dx.doi.org/10.1016/j.tranon.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006810PMC
August 2016

Proteomic analysis of halotolerant proteins under high and low salt stress in Dunaliella salina using two-dimensional differential in-gel electrophoresis.

Genet Mol Biol 2016 May;39(2):239-47

School of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China.

Dunaliella salina, a single-celled marine alga with extreme salt tolerance, is an important model organism for studying fundamental extremophile survival mechanisms and their potential practical applications. In this study, two-dimensional differential in-gel electrophoresis (2D-DIGE) was used to investigate the expression of halotolerant proteins under high (3 M NaCl) and low (0.75 M NaCl) salt concentrations. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatics were used to identify and characterize the differences among proteins. 2D-DIGE analysis revealed 141 protein spots that were significantly differentially expressed between the two salinities. Twenty-four differentially expressed protein spots were successfully identified by MALDI-TOF/TOF MS, including proteins in the following important categories: molecular chaperones, proteins involved in photosynthesis, proteins involved in respiration and proteins involved in amino acid synthesis. Expression levels of these proteins changed in response to the stress conditions, which suggests that they may be involved in the maintenance of intracellular osmotic pressure, cellular stress responses, physiological changes in metabolism, continuation of photosynthetic activity and other aspects of salt stress. The findings of this study enhance our understanding of the function and mechanisms of various proteins in salt stress.
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http://dx.doi.org/10.1590/1678-4685-GMB-2015-0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910558PMC
May 2016

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China.

Chin Med J (Engl) 2016 Feb;129(3):304-8

National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050; Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.

Background: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.

Methods: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.

Results: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).

Conclusion: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.

Trial Registration: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.
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http://dx.doi.org/10.4103/0366-6999.174509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799574PMC
February 2016

[Genome-wide identification and expression analysis of auxin-related gene families in grape].

Yi Chuan 2015 07;37(7):720-30

Institute of Horticulture, Jiangsu Academy of Agricultural Sciences/Jiangsu Key Laboratory for Horticultural Crop Genetic Improvement, Nanjing 210014, China.

The auxin response gene family adjusts the auxin balance and the growth hormone signaling pathways in plants. Using bioinformatics methods, the auxin-response genes from the grape genome database are identified and their chromosomal location, gene collinearity and phylogenetic analysis are performed. Probable genes include 25 AUX_IAA, 19 ARF, 9 GH3 and 42 LBD genes, which are unevenly distributed on all 19 chromosomes and some of them formed distinct tandem duplicate gene clusters. The available grape microarray databases show that all of the auxin-response genes are expressed in fruit and leaf buds, and significant overexpressed during fruit color-changing, bud break and bud dormancy periods. This paper provides a resource for functional studies of auxin-response genes in grape leaf and fruit development.
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http://dx.doi.org/10.16288/j.yczz.14-390DOI Listing
July 2015

Weight loss correlates with macrophage inhibitory cytokine-1 expression and might influence outcome in patients with advanced esophageal squamous cell carcinoma.

Asian Pac J Cancer Prev 2014 ;15(15):6047-52

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Fujian Province, China E-mail :

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC).

Materials And Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy: >5% weight loss group and≤5% weight loss group.

Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss>5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) CONCLUSIONS: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.
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http://dx.doi.org/10.7314/apjcp.2014.15.15.6047DOI Listing
January 2017

Neutrophil count and the inflammation-based glasgow prognostic score predict survival in patients with advanced gastric cancer receiving first-line chemotherapy.

Asian Pac J Cancer Prev 2014 ;15(2):945-50

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China E-mail :

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy.

Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS).

Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR , GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS.

Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.
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http://dx.doi.org/10.7314/apjcp.2014.15.2.945DOI Listing
November 2014

[Efficacy of albumin-bound paclitaxel in advanced gastric cancer patients].

Beijing Da Xue Xue Bao Yi Xue Ban 2014 Feb;46(1):144-8

Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Objective: To evaluate the safety and efficacy of albumin-bound paclitaxel in patients with advanced gastric cancer (AGC).

Methods: The patients with histopathologic or cytopathologic diagnosed advanced gastric cancer (AGC), Karnofsky performance status ≥ 60, and life expectancy >12 weeks, and with adequate organ functions of the bone marrow, liver, kidney and heart were recuited in our study. albumin-bound paclitaxel was administered alone or combined with capecitabine, TS-1, trastuzumab or cetuxizumb. The total doses of albumin-bound paclitaxel were 200-400 mg (130-260 mg/m(2)), divided on days 1, 8 or days 1,8, and 15, given intravenously during 30 minutes of a 21-day cycle. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The adverse events (AE) were graded according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC) 3.0 version.

Results: From July 2009 to Octobor 2012, the total of 25 patients were treated and completed 65 cycles of chemotherapy (median: 2 cycles, and range: 0.5-7). The median age was 57 years (range: 38-79). The majority of the patients were with non-gastroesophageal junction cancers and had metastasic disease with lymph nodes and peritoneum. Eleven patients were chemotherapy naive and the others had accepted previous systemic therapy for advanced disease. 16 patients were evaluable for clinical response. No complete response was observed and partial response (PR) was achieved in 5 patients. Five patients had stable disease and 6 patients progressed. Among the chemotherapy naive patients, 8 patients were evaluable for response, 3 patients had partial response (37.5%) and 1 patient had stable disease (tumor shrink). The clinical response rate was 50%. Time to treatment failure (TTF)was 3.7 months(95% CI 2.32-5.08) and time to death (TTD)was 7.9 months (95% CI 5.17-10.63). No statistical differences in TTF and TTD were observed between the untreated and the retreated patients or the monotherapy and the combination therapy groups. All the patients were suitable for safety assessment. Most toxicities were mild with grades 1/2. Hematologic AEs were more common with leucopenia and neutropenia. Meanwhile, nausea/vomiting, fatigue, peripheral neuropathy were the most common non-hematologic AEs. No allergic reaction or treatment-related deaths were recorded.

Conclusion: AGC patients could benefit from albumin-bound paclitaxel with lower dose level than breast cancer patients. Additional phase I/II studies of albumin-bound paclitaxel in gastric cancer are warranted.
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February 2014

Parameter estimation for metabolic networks with two stage Bregman regularization homotopy inversion algorithm.

J Theor Biol 2014 Feb 20;343:199-207. Epub 2013 Sep 20.

School of Computer Science and Technology, Dalian University of Technology, Dalian, China; State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian, China. Electronic address:

Metabolism is a very important cellular process and its malfunction contributes to human disease. Therefore, building dynamic models for metabolic networks with experimental data in order to analyze biological process rationally has attracted a lot of attention. Owing to the technical limitations, some unknown parameters contained in models need to be estimated effectively by means of the computational method. Generally, problems of parameter estimation of nonlinear biological network are known to be ill condition and multimodal. In particular, with the increasing amount and enlarging the scope of parameters, many optimization algorithms often fail to find a global solution. In this paper, two-stage variable factor Bregman regularization homotopy method is proposed. Discrete homotopy is used to identify the possible extreme region and continuous homotopy is executed for the purpose of stability of path tracing in the special region. Meanwhile, Latin hypercube sampling is introduced to get the good initial guess value and a perturbation strategy is developed to jump out of the local optimum. Three metabolic network inverse problems are investigated to demonstrate the effectiveness of the proposed method.
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http://dx.doi.org/10.1016/j.jtbi.2013.09.020DOI Listing
February 2014

[Correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2013 Jun;16(6):524-8

Department of Gastrointestinal Oncology, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China.

Objective: To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).

Methods: Clinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.

Results: Allele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.

Conclusion: MDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.
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June 2013

Expressions of Thymidylate Synthase,Thymidine Phosphorylase, Class III β-tubulin, and Excision Repair Cross-complementing Group 1predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin.

Chin J Cancer Res 2011 Dec;23(4):288-94

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, PekingUniversitySchool of Oncology, BeijingCancerHospital& Institute, Beijing 100142, China.

Objective: Toevaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin.

Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically.

Results: The median age of 57 patients was 57 years (range: 27-75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361).

Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.
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http://dx.doi.org/10.1007/s11670-011-0288-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551314PMC
December 2011

Asymptomatic oral yeast carriage and antifungal susceptibility profile of HIV-infected patients in Kunming, Yunnan Province of China.

BMC Infect Dis 2013 Jan 28;13:46. Epub 2013 Jan 28.

Department of Dermatology and Venereology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.

Background: Oral Candida colonization and its relation with predisposing factors in HIV-infected patients have received wide concerns during recent decades. In this study, we investigated asymptomatic oral Candida carriage rate, species distribution and antifungal susceptibility of 604 HIV-infected patients and 851 healthy individuals in Kunming, Yunnan Province of China.

Methods: Mucosal swab sampling was taken from each subject and CHROMagar Candida agar medium and API 20C AUX system were used to identify yeast isolates. In vitro antifungal susceptibility was tested by the broth microdilution method according to the M27-A2 document of the Clinical and Laboratory Standard Institute (CLSI).

Results: The oral yeast colonization rate in HIV-infected patients (49.5%) was higher than that of healthy subjects (20.7%). Candida albicans constituted the most frequent species, accounting for 82.2% of yeast isolates. The remaining species were composed of C. glabrata, C. parapsilosis, C. krusei, C. tropicalis, C. rugosa, C. norvegensis, Pichia ohmeri and Saccharomyces cerevisiae. In HIV-infected patients, asymptomatic oral yeast colonization was associated with low CD4 cell count (<200 cells/mm3) and lack of highly active antiretroviral therapy (HAART). Different Candida species isolated from our samples presented different susceptibility to voriconazole, fluconazole and itraconazole. Amphotericin B had the best inhibiting effect for all isolates.

Conclusion: Oral yeast colonization in Han Chinese patients with HIV from Kunming had common and unique features and was associated with CD4 cell number and HARRT. Amphotericin B should be used with first priority in controlling Candida infection in Han Chinese patients from Kunming. Our results provide first hand information on monitoring oral yeasts colonization in HIV-infected patients from Kunming, China.
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http://dx.doi.org/10.1186/1471-2334-13-46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641955PMC
January 2013

Analysis of expressed sequence tags from grapevine flower and fruit and development of simple sequence repeat markers.

Mol Biol Rep 2012 Jun 9;39(6):6825-34. Epub 2012 Feb 9.

College of Horticulture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.

A total of 6,230 EST sequences were produced from 7,561 clones in a cDNA library generated from grapevine (Vitis vinifera cv. 'Summer Black') flower and fruit tissues in this study. After cluster and assembly analysis of the datasets, 3,582 unigenes (GenBank accession numbers GW836604-GW840185) were established, among which 381 were new grapevine EST sequences. Out of the 381 new ESTs, 289 could be mapped on the 19 grapevine chromosomes. 913 unique ESTs with known or putative functions were assigned to 11 putative cellular roles. 540 potentially workable grapevine EST-SSRs were developed from 3,582 unigenes and about 42.6% of these unigenes were identified as true-to-type SSR loci and could amplify polymorphic bands from 22 individual plants of V. vinifera L, indicating that grapevine EST datasets are a valuable source for the development of functional simple sequence repeat (SSR) markers.
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http://dx.doi.org/10.1007/s11033-012-1507-1DOI Listing
June 2012

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis.

Nan Fang Yi Ke Da Xue Xue Bao 2011 Jun;31(7):1114-8

Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.

Objective: To evaluate the efficacy and toxicity of the combined chemotherapy with docetaxel, capecitabine and cisplatin (TXP) in the treatment of metastatic nasopharyngeal carcinoma (NPC).

Methods: This retrospective analysis involved 22 patients with metastatic NPC receiving treatment with the TXP regimen. The patients were given docetaxel at 60 mg/m² on day 1, cisplatin at 20 mg/m² on days 1-3, and capecitabine at 1 250 mg/m² on days 1-14, and the treatment cycle was repeated ever 3 weeks.

Results: Of the 22 patients, 14 (63%) achieved partial remission, 2 (9%) had complete remission, and 5 (23%) showed stable disease. The overall clinical response rate of the patients was 72% with a 1-year survival rate of 68%, median progression-free survival of 8 months, and overall survival of 14 months. The main toxicity was myelosuppression; 7 (32%) patients experienced grade 3/4 neutropenia, and 5 (23%) had grade 3/4 anemia. All the other adverse effects were tolerable and reversible.

Conclusion: The TXP regimen is safe and effective for treatment of metastatic NPC, and the results are comparable with those of the reports in recent literatures.
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June 2011

Clinical analysis of skin lesions in 796 Chinese HIV- positive patients.

Acta Derm Venereol 2011 Sep;91(5):552-6

STD and AIDS Clinical Center, Beijing Youan Hospital, Capital Medical University, China.

Skin lesions are often associated with human immunodeficiency virus (HIV) infection, reflecting the immunocompromised status of the individual. We investigated the relationship between skin lesions and immune function in a retrospective study of 796 Chinese HIV patients with and without highly active antiretroviral therapy (HAART). Of the 651 patients who had not received HAART, we found that 531 (81.6%) had apparent skin lesions. The incidence of infectious skin diseases (fungi, viruses, bacteria, spirochetes and parasites) and non-infectious skin diseases (excluding skin cancer) was 68.8% and 34.9%, respectively. Mean CD4(+) T-cell counts and CD4(+)/CD8(+) ratios were lower in patients with skin lesions than in patients without lesions (178 ± 96/µl vs. 306 ± 189/µl (p < 0.05) and 0.22 vs. 0.34 (p < 0.01), respectively). Candidiasis (25.8%), eczema (19.2%), nodular prurigo (13.8%), dermatophyte infections (10.6%) and herpes zoster (9.4%) were most common in Chinese patients with HIV. Among the 145 patients who had started HAART, there was a significantly lower prevalence of skin diseases (29.0%), although drug eruptions (12.4%) were more commonly observed. These findings indicate that HAART often reduces the incidence of infectious and non-infectious skin lesions in patients with HIV, but can itself be the cause of drug eruptions.
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http://dx.doi.org/10.2340/00015555-1107DOI Listing
September 2011
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