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ESTROGEN REGULATION OF LRP16 GENE EXPRESSION INVOLVES SP1 TRANSCRIPTION FACTOR

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Chinese Journal of Cancer Research 2006年第4期18卷 251-256页

作者：司艺玲韩为东赵亚力李琦郝好杰宋海静母义明于力 Department of Molecular biology Institute of Basic Medicine PLA General Hospital Department of Molecular biology Institute of Basic Medicine PLA General Hospital Department of Endocrinology PLA General Hospital Department of hematology PLA General Hospital

Objective： To investigate the role of Spl as transcription factor required for transactivation of LRP16 gene by estrogen. Methods： Specific antibodies of ERα and Spl were used to precipitate the target DNA/protein complexes of MCF-7 cells at different time points after estrogen treatment （Chromatin immunoprecipitation assay）, the promoter region of LRP16 gene was amplified by semi-nested polymerase chain reaction （snPCR）. Small interfering RNA （siRNA） against Spl was transiently cotransfected with LRP16-Luc （containing the region from -213bp to -126bp of LRP16 gene promoter）in MCF-7 cells. The luciferase activities were measured by dual-luciferase assay. Results： The results of chromatin immunoprecipitation assay showed that Spl protein directly bound to the -213bp to -126bp region of LRP16 gene, and ERα could enhance the affinity of Spl to DNA. Spl-siRNA specifically decreased the transactivation of LRP16-Luc by 1713-estradio1 to 70-80%. Conclusion： The estrogen-induced transactivation of the human LRP16 gene was mediated by Spl protein. Moreover, the interactions of ERα/Sp1 functional complex with LRP16 promoter DNA were required for enhanced LRP16 gene transactivation.

关键词： Sp1 LRP16 gene Small interference RNA Estrogen Gene expression

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

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World Journal of Gastroenterology 2021年第35期27卷 5932-5945页

作者： Michael D Diamantidis Maria Papaioannou Evdoxia Hatjiharissi Department of hematology Thalassemia and Sickle Cell Disease UnitGeneral Hospital of LarissaLarissa 41221ThessalyGreece Division of hematology First Department of Internal MedicineAHEPA General HospitalAristotle University of ThessalonikiThessaloniki 54636Greece

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and *** main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma *** has been one of the main fields of clinical research of our group in recent *** gastric DLBCLs are frequent,sufficient data to guide optimal care are *** today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these *** this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published *** then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective *** to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in *** study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was *** the next 2 mo,we will present the update of our study with the same basic conclusion.

关键词： Primary gastric lymphoma Extranodal non-Hodgkin’s lymphoma Diffuse large B-cell lymphoma Mucosa-associated lymphoid tissue Immunochemotherapy Rituximab-cyclophosphamide doxorubicin vincristine prednisone

Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment

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Cellular & Molecular Immunology 2020年第4期17卷 430-432页

作者： Yelei Guo Kaichao Feng Chuan Tong Hejin Jia Yang Liu Yao Wang Dongdong Ti Qingming Yang Zhiqiang Wu Weidong Han Department of Molecular biology and Immunology Chinese PLA General HospitalBeijingChina Department of Bio-therapeutic Chinese PLA General HospitalBeijingChina Department of Geriatric hematology Chinese PLA General HospitalBeijingChina

(CAR)T cells and immune checkpoint blockade therapies has shown remarkable outcomes in the field of cancer treatment.1,2 In particular,great success has been achieved in B cell acute lymphocytic leukemia(B-ALL)treated with anti-CD19 CAR T cells.2 However,the loss,mutation,and reduced expression of CD19 are crucial causes for the failure of CAR T cell treatment in leukemia patients.3,4 CD38,a 45-kDa type II glycoprotein,is detectable in BALL,and several studies have indicated the efficacy and safety of CD38 monoclonal antibodies in clinical applications,suggesting that CD38 represents a suitable therapeutic target for the treatment of B-ALL.5,6 In addition,we developed a CAR against CD38,and our preclinical study indicated that anti-CD38 CAR T(CAR T-38)cells could specifically lyse CD38-positive tumor cells.7 Herein,we present the anti-leukemia ability of CAR T-38 cells in an adult relapsed B-ALL patient after failure of bi-specific CD19/CD22 CAR T cell treatment,and this administration of CAR T-38 cells was accompanied by the occurrence of target-mediated toxicities and severe and uncontrollable cytokine release syndrome(CRS).

关键词： CD38 CD22 CD19 treatment

Construction and Significance of Directional Expression cDNA Library from Human NB4 Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第1期24卷 52-54,58页

作者：陈刚张王刚付杰曹星梅赵万红韩月恒赵爱志李福洋刘新平药立波 Department Of hematology Department Of Biochemistry and Molecular biology

Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR Ⅰ adapters. Then the cDNAs were digested with Xho Ⅰ, and less than 400 bp cDNA fragment was removed by Sephacryl S400 spin column, the remaining were ligated with λZAP vector. The recombinants were packaged in vitro , and a small portion of packaged phage was used to infect E. coli XL1 Blue MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK CMV phagemid was digested by Xho Ⅰ and EcoR Ⅰ. The results showed that the NB4 cell line cDNA library consisting of 1.65×10 6 recombinant bacteriophages was constructed with the recombinant ratio of 99.6 %. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.

关键词： acute premyeloid leukemia NB4 cells cDNA library

A case of successful management with splenectomy of intractable ascites due to congenital dyserythropoietic anemia type II-induced cirrhosis

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World Journal of Gastroenterology 2006年第5期12卷 818-821页

作者： Themistoklis Vassiliadis Vassilia Garipidou Vassilios Perifanis Konstantinos Tziomalos OIga Giouleme Kalliopi Patsiaoura Michalis Avramidis Nikolaos Nikolaidis Sofia Vakalopoulou Ioannis Tsitouridis Antonios Antoniadis Panagiotis Semertzidis Anna Kioumi Evangelos Premetis Nikolaos Eugenidis 2~(nd) Propedeutic Department of Internal Medicine Aristotle University of ThessalonikiHippokration General HospitalThessalonikiGreece Department of Pathology Hippokration General HospitalThessalonikiGreece Department of Radiology Papageorgiou General HospitalThessalonikiGreece Organ Transplant unit Aristotle University of ThessalonikiHippokration General HospitalThessalonikiGreece Department of hematology Papageorgiou General Hospital Thessaloniki Greece hematology Laboratory Aghia Sophia Children's HospitalAthensGreece

The congenital dyserythropoietic anemias comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by characteristic morphological aberrations of the majority of erythroblasts in the bone marrow. Congenital dyserythropoietic anemia type II is the most frequent type. All types of congenital dyserythropoietic anemias distinctly share a high incidence of iron loading. Iron accumulation occurs even in untransfused patients and can result in heart failure and liver cirrhosis. We have reported about a patient who presented with liver cirrhosis and intractable ascites caused by congenital dyserythropoietic anemia type II. Her clinical course was further complicated by the development of autoimmune hemolytic anemia. Splenectomy was eventually performed which achieved complete resolution of ascites, increase of hemoglobin concentration and abrogation of transfusion requirements.

关键词： Portosystemic shunt Hemosiderosis Splenectomy Intractable ascites Congenital dyserythropoietic anemia type Ⅱ

Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 341-347页

作者： Philip J Saylor Division of hematology-Oncology Massachusetts General Hospital Cancer Center Boston Massachusetts USA.

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-K-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

关键词： denosumab osteoporosis osteopenia osteoclast RANK (receptor activator of nuclear factor-kappa B) skeletal-relatedevents

An exceptional case of myelodysplastic syndrome with myelofibrosis following combination chemotherapy for squamous cell lung cancer

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Cancer biology & Medicine 2013年第2期10卷 117-120页

作者： Yi-Hao Wang Rong Fu Zong-Hong Shao Department of hematology Tianjin Medical University General Hospital

A 60-year-old woman with squamous cell carcinoma in the right lung was successfully treated with four cycles of combination chemotherapy after surgery, and complete remission was achieved. However, the patient developed myelodysplastic syndrome (MDS) RAEB-2 with myelofibrosis after remission, possibly because of chemotherapy or DNA methylation. The patient responded well to dacitabine (Dacogen), suggesting that DNA hypomethylation agents can be a promising therapy to retard the progression of a second tumor or carcinoma.

关键词： DNA methylation myelodysplastic syndrome myelofibrosis squamous cell lung cancer

Expression of DLK1 Gene in the Bone Marrow Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significance

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Clinical oncology and cancer researeh 2012年第3期9卷 188-191页

作者： Lan-zhu Yue Rong Fu Hua-quan Wang Li-juan Li Er-bao Ruan Guo-jin Wang Wen Qu Yong Liang Jing Guan Yu-hong Wu Hong Liu Jia Song Xiao-ming Wang Li-min Xing Zong-hong Shao Department of hematology General Hospital of Tianjin Medical University

Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia （AML）, and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients （0.7342±0.3652） compared with the normal control group （0.4801±0.1759）（P〈0.05）. The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts （r=0.467, P〈0.05）. Moreover, DLK1 mRNA expression was significantly increased as MDS progressed （P〈0.05）. Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA （0.9007±0.4334） than those with normal karyotypes （0.6411±0.2630）（P〈0.05）. Subsequently, patients with highly expressed DLK1 （≥0.8） presented significantly higher malignant clone burden （0.4134±0.3999） than those with lower DLK1 expression （〈0.8）,（0.1517±0.3109）, （P〈0.05）. Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.

关键词： DLK1 gene myelodysplastic syndromes expression

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

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Clinical oncology and cancer researeh 2012年第1期9卷 73-76页

作者： Kai Ding Xiao-ming Wang Rong Fu Er-bao Ruan Hui Liu Zong-hong Shao Department of hematology General Hospital of Tianjin Medical University

Objective To investigate the expression of the preferentially expressed antigen of melanoma （PRAME） gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia （AL） and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics （gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype） of the patients were performed. Results The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia （AML, n=27）, and in 28.6% of the patients with acute lymphoblastic leukemia （ALL, n=7）, but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M~, 33.3% in M2, and 28.6% in M~. Gene expression was also found to be correlated with CDl5 and CD33 expression and abnormal karyotype, but not with age, gender; white blood count or percentage of blast cells. Conclusions The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia.

关键词： preferentially expressed antigen of melanoma gene acute leukemia minimal residual disease immunotherapy