Central Hospital of Karamay

Karamay, China

Central Hospital of Karamay

Karamay, China
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Zhang X.,Peking Union Medical College | Yang Y.,Peking Union Medical College | Zhang L.,Peking Union Medical College | Lu Y.,Peking Union Medical College | And 6 more authors.
Journal of Hematology and Oncology | Year: 2017

Background: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration. Methods: Human umbilical cord-derived MSCs (UC-MSCs) were genetically modified to secrete Tandab (CD3/CD19), a tetravalent bispecific tandem diabody with two binding sites for CD3 and two for CD19. The tropism of MSCs towards Raji cells in vitro was determined by migration assays, and the homing property of MSCs in vivo was analyzed with firefly luciferase-labeled MSCs (MSC-Luc) by bioluminescent imaging (BLI). The cytotoxicity of T cells induced by MSC-secreting Tandab (CD3/CD19) was detected in vitro and in vivo in combination with d-1-methyl-tryptophan (D-1MT), an IDO pathway inhibitor. Results: The purified Tandab (CD3/CD19) was functional with high-binding capability both for CD3-positive cells and CD19-positive cells and was able to induce specific lysis of CD19-positive cell lines (Raji, Daudi, and BJAB) in the presence of T cells. Additionally, results from co-culture killing experiments demonstrated that Tandab (CD3/CD19) secreted from MSCs was also effective. Then, we confirmed that D-1MT could enhance the cytotoxicity of T cells triggered by MSC-Tandab through reversing T cell anergy with down-regulation of CD98 and Jumonji and restoring the proliferation capacity of T cells. Furthermore, MSC-Luc could selectively migrate to tumor site in a BALB/c nude mouse model with Raji cells. And mice injected with MSC-Tandab in combination with D-1MT significantly inhibited the tumor growth. Conclusions: These results suggest that UC-MSCs releasing Tandab (CD3/CD19) is an efficient therapeutic tool for the treatment of B cell lymphoma when combined with D-1MT. © 2017 The Author(s).


Li Z.,Peking Union Medical College | Li Z.,Xi'an Jiaotong University | Ye Z.,Central Hospital of Karamay | Zhang X.,Peking Union Medical College | And 7 more authors.
Oncotarget | Year: 2016

Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A infection could specifically migrate to HepG2 tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of 5-fluorouracil (5-Fu), because the expression levels of coxsackie adenovirus receptor (CAR) and integrin αvβ3 on tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-tumor activity in vivo, particularly in combination with low doses of 5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the tumor tropism of HUMSCs, to improve the outcome of virotherapy for tumor patients especially those with metastatic diseases.


Peng H.,Nanchang University | Peng H.,Peking Union Medical College | Yuan X.,Peking Union Medical College | Luo S.,Nanchang University | And 4 more authors.
European Journal of Pharmacology | Year: 2014

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells and is verified to be effective in various cancers. However, a variety of cancer cells are found to be resistant to TRAIL and the mechanisms are largely unknown. Moreover, multidrug resistance to traditional chemotherapeutic agents still remains a tough problem in clinical practice. Fortunately, our previous work proved the ability of PH II-7 in overcoming MDR phenotype through reactive oxygen species production in K562 and its MDR counterpart K562/A02 cells. Additionally, we further explored its potential in augmenting TRAIL induced apoptosis in cancer cells with various tissue origins. Our results showed PH II-7 up-regulated DR4/DR5 expression and augment TRAIL cytotoxicity through reactive oxygen species production, which provide a solid foundation for TRAIL in combination with PH II-7 in future clinical application. © 2014 Elsevier B.V. All rights reserved.


PubMed | Central Hospital of Karamay, Xi'an Jiaotong University, Harvard University and Peking Union Medical College
Type: Journal Article | Journal: Oncotarget | Year: 2016

Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A infection could specifically migrate to HepG2 tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of 5-fluorouracil (5-Fu), because the expression levels of coxsackie adenovirus receptor (CAR) and integrin 3 on tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-tumor activity in vivo, particularly in combination with low doses of 5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the tumor tropism of HUMSCs, to improve the outcome of virotherapy for tumor patients especially those with metastatic diseases.


PubMed | Central Hospital of Karamay, Tianjin Medical University and Peking Union Medical College
Type: | Journal: Journal of hematology & oncology | Year: 2015

Leukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (IL3)-receptor chain, has been identified as a potential immunotherapeutic target due to its overexpression on LSCs in AML as well as on AML blasts, rather than normal hematopoietic stem cells.We constructed a CD123-targeted fusion protein antiCD3Fv-IL3, with one binding site for T cell antigen receptor (TCRCD3) and the other for CD123, by recombinant gene-engineering technology. Cysteine residues were introduced into the V domains of the antiCD3Fv segment to enhance its stability by locking the two chains of Fv together with disulfide covalent bonds. The stability and cytotoxicity of the two fusion proteins were detected in vitro and in vivo.Both fusion proteins were produced and purified from Escherichia coli 16C9 cells with excellent yields in fully active forms. High-binding capability was observed between these two fusion proteins and human IL3R, leading to the specific lysis of CD123-expressing cell lines KG1a; also, mononuclear cells from primary AML patients were inhibited in a colony forming assay in vitro, presumably by redirecting T lymphocytes in vitro. In addition, they displayed an antileukemic activity against KG1a xenografts in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, especially disulfide-stabilized (ds)-antiCD3Fv-IL3 for its improved stability.These results suggest that both fusion proteins display the antileukemic activity against CD123-expressing cell lines as well as leukemic progenitors in vitro and in vivo, especially ds-antiCD3Fv-IL3. They could be the promising candidates for future immunotherapy of AML.


Han W.,Central Hospital of Karamay
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics | Year: 2011

To study the prognosis of childhood asthma and the factors influencing asthmatic attacks and prognosis. The medical data of 212 children with asthma who were followed up for more than 5 years were retrospectively studied. During the 5-year follow up, asthmatic attacks termination was found in 121 cases (57.1%) and asthma persistence was observed in 91 cases. Respiratory tract infections were found as the major factors inducing asthmatic attacks (71.7%), followed by inhaled allergens (17.0%).The children with asthma induced by respiratory tract infections had a higher remission rate of asthmatic attacks (61.2%) than those induced by allergens (41.7%) or exercises (26.3%). Three risk factors for asthma persistence were identified: concurrent allergic rhinitis and eczema, parental asthma and allergy-induced wheezing. The 5-year follow-up study demonstrated that asthmatic attacks stopped in the majority of children with asthma. Respiratory tract infections may be the major factors inducing acute asthma attacks. The children with asthma induced by respiratory infections may experience a better outcome. Atopic children or children with the genetic background of atopy are at high risks for the development of persistent asthma.


Ma C.,Xinjiang Medical University | Deng Q.,Xinjiang Medical University | Pu H.,Xinjiang Medical University | Cheng X.,Peoples Hospital of the Xinjiang Uygur Autonomous Region | And 4 more authors.
Bone Research | Year: 2016

The purpose of this study was to compare the functional outcomes, psychological impact, and complication rates associated with external fixation and volar or dorsal plating in relation to the functional parameters following treatment of intra-articular fractures of the distal radius (IFDR) in patients older than 65 years. We hypothesized that using volar or dorsal plating would improve functional outcomes, but that it would be associated with more complications and equivalent functional outcomes when compared with the external fixation group. A total of 123 consecutive patients suffering from IFDR were recruited into the study. The patients were measured for clinical, radiological, and psychosocial functioning outcomes and were followed up after 1 week and 3, 6 and 12 months. After 3 months, the plating group had better pronation (P=0.001), supination, (P=0.047) and extension (P=0.043) scores. These differences were somewhat attenuated by 6 months and disappeared at 1 year. The plating group had a greater occurrence of wound infection (P=0.043), tendonitis, (P=0.024) and additional surgery compared with the external fixation group. The only TNO-AZL Adult Quality of Life scores in the plating group that were lower than those in the external fixation group were in the "gross motor" category (walking upstairs, bending over, walking 500 yards; P=0.023). Internal fixation was more advantageous than external fixation in the early rehabilitation period; after 1 year the outcomes were similar. The plating group showed significantly higher levels of wound infection and tendonitis and had a greater need for additional surgeries. © 2016 The Author(s).


Fan D.,Chinese Academy of Sciences | Li Z.,Chinese Academy of Sciences | Zhang X.,Chinese Academy of Sciences | Yang Y.,Tianjin Medical University | And 4 more authors.
Journal of Hematology and Oncology | Year: 2015

Background: Leukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (IL3)-receptor α chain, has been identified as a potential immunotherapeutic target due to its overexpression on LSCs in AML as well as on AML blasts, rather than normal hematopoietic stem cells. Methods: We constructed a CD123-targeted fusion protein antiCD3Fv-δIL3, with one binding site for T cell antigen receptor (TCRCD3) and the other for CD123, by recombinant gene-engineering technology. Cysteine residues were introduced into the V domains of the antiCD3Fv segment to enhance its stability by locking the two chains of Fv together with disulfide covalent bonds. The stability and cytotoxicity of the two fusion proteins were detected in vitro and in vivo. Results: Both fusion proteins were produced and purified from Escherichia coli 16C9 cells with excellent yields in fully active forms. High-binding capability was observed between these two fusion proteins and human IL3R, leading to the specific lysis of CD123-expressing cell lines KG1a; also, mononuclear cells from primary AML patients were inhibited in a colony forming assay in vitro, presumably by redirecting T lymphocytes in vitro. In addition, they displayed an antileukemic activity against KG1a xenografts in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, especially disulfide-stabilized (ds)-antiCD3Fv-δIL3 for its improved stability. Conclusions: These results suggest that both fusion proteins display the antileukemic activity against CD123-expressing cell lines as well as leukemic progenitors in vitro and in vivo, especially ds-antiCD3Fv-δIL3. They could be the promising candidates for future immunotherapy of AML. © 2015 Dongmei et al.; licensee BioMed Central.


Han W.,Central Hospital of Karamay | Xie Y.,Central Hospital of Karamay | Ren S.-Y.,Central Hospital of Karamay | Yin L.-M.,Central Hospital of Karamay | And 3 more authors.
Chinese Journal of Contemporary Pediatrics | Year: 2014

Objective: To study the clinical significance of tidal breathing lung function test in 1-4 years old children with wheezing diseases. Methods: A total of 141 1-4 years old children with wheezing diseases were enrolled as the observed groups (41 cases of asthma, 54 cases of asthmatic bronchitis, and 46 cases of bronchopneumonia). Thirty children without respiratory diseases were enrolled as the control group. All the recruits underwent tidal breathing lung function test. The observed groups underwent bronchial dilation test, and tidal breathing flow volume (TBFV) parameters were evaluated before and after bronchial dilation test. Results: The observed groups showed obstructive ventilatory disorder (65%) according to the TBFV loop, and their ratio of time to peak tidal expiratory flow (TPTEF) to total expiratory time (TE) and ratio of volume to peak expiratory flow (VPEF) to total expiratory volume (VE) were significantly lower than in the control group (P<0.05). The asthma subgroup had significantly improved TPTEF/TE and VPEF/VE after bronchial dilation test (P<0.05). Taking an improvement rate of ≥15% either for TPTEF/TE or for VPEF/VE as an indicator of positive bronchial dilation test, the bronchial dilation test had a sensitivity of 47% and a specificity of 84% in diagnosing asthma in 1-4 years old children. The positive rate was 28% among the children in the asthma subgroup with an TPTEF/TE ratio of ≥23% before bronchial dilation test, versus 65% in those with an TPTEF/TE ratio of <23%. Conclusions: Obstructive ventilatory disorder is the main impairment of tidal breathing lung function in 1-4 years old children with wheezing diseases. Tidal breathing bronchial dilation test can reflect a reversal of airway obstruction to a certain extent. The sensitivity of bronchial dilation test for the diagnosis of asthma is not satisfactory in 1-4 years old children with wheezing diseases, but this test has a relatively high diagnostic value in children with severe airway obstruction.


PubMed | Central Hospital of Karamay
Type: Journal Article | Journal: Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics | Year: 2014

To study the clinical significance of tidal breathing lung function test in 1-4 years old children with wheezing diseases.A total of 141 1-4 years old children with wheezing diseases were enrolled as the observed groups (41 cases of asthma, 54 cases of asthmatic bronchitis, and 46 cases of bronchopneumonia). Thirty children without respiratory diseases were enrolled as the control group. All the recruits underwent tidal breathing lung function test. The observed groups underwent bronchial dilation test, and tidal breathing flow volume (TBFV) parameters were evaluated before and after bronchial dilation test.The observed groups showed obstructive ventilatory disorder (65%) according to the TBFV loop, and their ratio of time to peak tidal expiratory flow (TPTEF) to total expiratory time (TE) and ratio of volume to peak expiratory flow (VPEF) to total expiratory volume (VE) were significantly lower than in the control group (P<0.05). The asthma subgroup had significantly improved TPTEF/TE and VPEF/VE after bronchial dilation test (P<0.05). Taking an improvement rate of 15% either for TPTEF/TE or for VPEF/VE as an indicator of positive bronchial dilation test, the bronchial dilation test had a sensitivity of 47% and a specificity of 84% in diagnosing asthma in 1-4 years old children. The positive rate was 28% among the children in the asthma subgroup with an TPTEF/TE ratio of 23% before bronchial dilation test, versus 65% in those with an TPTEF/TE ratio of <23%.Obstructive ventilatory disorder is the main impairment of tidal breathing lung function in 1-4 years old children with wheezing diseases. Tidal breathing bronchial dilation test can reflect a reversal of airway obstruction to a certain extent. The sensitivity of bronchial dilation test for the diagnosis of asthma is not satisfactory in 1-4 years old children with wheezing diseases, but this test has a relatively high diagnostic value in children with severe airway obstruction.

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