1.CIC-rearranged sarcoma: a clinicopathological analysis of four cases.
Xin WAN ; Jin Ling TANG ; Xiao LI ; Cong WANG ; Hai LI ; Min Hong PAN
Chinese Journal of Pathology 2023;52(7):690-695
Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.
Repressor Proteins/genetics*
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Sarcoma/therapy*
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Humans
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Male
;
Female
;
Adult
2.Construction and phenotypic study of Pseudomonas aeruginosa inducibly expressing a ferric uptake regulator.
Zhipeng WANG ; Haiying YU ; Lüyan MA
Chinese Journal of Biotechnology 2021;37(9):3253-3267
Members of the ferric uptake regulator (Fur) protein family are bacterial transcriptional repressors that control iron uptake and storage in response to iron availability, thereby playing a crucial role in the maintenance of iron homeostasis. The fur null mutants of Pseudomonas aeruginosa could not be obtained because fur is an essential gene. In this study, We constructed a Fur inducibly expression strain Δfur/attB::PBAD-fur in order to study the effect of fur on the growth, biofilm formation, motilities and oxidative stress response of P. aeruginosa. The results showed that a low level of fur expression retarded the growth of P. aeruginosa at an iron-depleted condition, or under high concentration of iron, or in the presence of H2O2. Fur affected the biofilm formation and the motilities (swimming, twitching, and swarming) of strain PAO1. The production of pyoverdine is regulated by Fur. Interestingly, proteins from Magnetospirillum gryphiswaldense MSR-1, which shares homology with Fur, can partially recover the pyoverdine production of strain Δfur/attB::PBAD-fur. This study provides new clues for the prevention and treatment of P. aeruginosa infections.
Bacterial Proteins/genetics*
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Hydrogen Peroxide
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Magnetospirillum
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Pseudomonas aeruginosa/genetics*
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Repressor Proteins/genetics*
3.The role of nuclear receptor transcription factor NR2F6 in tumor.
Ling HUANG ; Jiahui LIU ; Yi ZHU ; Quan ZHOU ; Bin XIAO ; Zhaohui SUN ; Linhai LI
Chinese Journal of Biotechnology 2021;37(8):2595-2602
Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.
Gene Expression Regulation
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Humans
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Neoplasms/genetics*
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Receptors, Cytoplasmic and Nuclear/genetics*
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Repressor Proteins/genetics*
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Transcription Factors/genetics*
4.Characterization of Cell Subsets Associated With Prognosis of Osteosarcoma Based on Single-Cell Sequencing Data.
Sheng-Tao WANG ; Hao-Ran ZHU ; Shu-Juan XU ; Peng GUI ; Ming-Zhou CHEN ; Zhao-Xu LI
Acta Academiae Medicinae Sinicae 2023;45(5):773-782
Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Humans
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Prognosis
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Osteosarcoma/genetics*
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Immunotherapy
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Macrophages
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Transcription Factors
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Bone Neoplasms/genetics*
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Homeodomain Proteins
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Repressor Proteins
6.A pedigree affected with spinocerebellar ataxia type III.
Chinese Journal of Medical Genetics 2017;34(3):463-464
Adult
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Ataxin-3
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genetics
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Female
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Humans
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Male
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Middle Aged
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Pedigree
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Repressor Proteins
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genetics
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Spinocerebellar Ataxias
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genetics
7.Influence of nagE and manX knockout with red homologous recombination on the microbial production of glucosamine by Escherichia coli.
Xin CHEN ; Long LIU ; Jianghua LI ; Jie LIU ; Guocheng DU ; Jian CHEN
Chinese Journal of Biotechnology 2012;28(3):305-319
Glucosamine (GlcN), also called amino sugar, is a compound derived from the substitution of a hydroxyl group of glucose molecule with an amino group. GlcN finds a wide-range of applications in health food and pharmaceutical industries. In our previous research, a recombinant Escherichia coli-glms-gnal was constructed for the efficient production of GlcN and N-acetylglucosamine (GlcNAc), the latter can be readily deacetylated to GlcN under mild acidic conditions. However, the results indicated that the titer of GlcN and GlcNAc decreased significantly due to the transportation of GlcN and GlcNAc from the culture broth to the inside of cells. To alleviate or block the transportation process, nagE gene (encoding for the GlcNAc-specific transporter) and manX gene (encoding for the mannose transporter) were knocked out with the Red homologous recombination method, and two engineered strains, E. coli-glms-gna1-delta nagE (with nagE gene deletion) and E. coli-glms-gna1-delta nagE-delta manX (with nagE and manX genes deletion), were successfully constructed. The two strains were cultured in a 7-L fermentor for the production of GlcN and GlcNAc. The maximal GlcN concentration of control strain E. coli-glms-gnal reached 4.06 g/L, and the maximal GlcNAc concentration reached 41.46 g/L. The maximal GlcN and GlcNAc concentration of E. coli-glms-gna1-delta nagE reached 4.38 g/L and 71.80 g/L, respectively, which were 1.08-fold and 1.70-fold of those of E. coli-glms-gnal, respectively. The maximal GlcN and GlcNAc concentration of E. coli-glms-gnal-delta nagE-delta manX reached 4.82 g/L and 118.78 g/L, respectively, which were 1.20-fold and 2.86-fold of those of E. coli-glms-gnal, respectively. These results suggested that the deletion of nagE and manX could significantly increase the extracellular accumulation of GlcN and GlcNAc. The results obtained here maybe useful for the microbial GlcN production in an industrial scale.
Acetylglucosamine
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biosynthesis
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genetics
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Escherichia coli
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genetics
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metabolism
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Escherichia coli Proteins
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genetics
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Gene Knockout Techniques
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Glucosamine
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biosynthesis
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genetics
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Repressor Proteins
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genetics
8.From azoospermia to macrozoospermia, a phenotypic continuum due to mutations in the ZMYND15 gene.
Zine-Eddine KHERRAF ; Caroline CAZIN ; Florence LESTRADE ; Jana MURONOVA ; Charles COUTTON ; Christophe ARNOULT ; Nicolas THIERRY-MIEG ; Pierre F RAY
Asian Journal of Andrology 2022;24(3):243-247
Thanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (AURKC gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia. AURKC analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (ZMYND15 gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man, ZMYND15 has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic ZMYND15 variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in ZMYND15 can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific AURKC or dpy-19 like 2 (DPY19L2) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES.
Animals
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Azoospermia/genetics*
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Humans
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Infertility, Male/genetics*
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Male
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Membrane Proteins/genetics*
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Mice
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Mutation
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Oligospermia/genetics*
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Repressor Proteins/metabolism*
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Teratozoospermia/genetics*
10.The diagnostic value of CCNB3 and BCOR expression in BCOR-CCNB3 sarcoma.
Lan LI ; Ming ZHANG ; Xiao Qi SUN ; Ting Ting ZHANG ; Yi DING
Chinese Journal of Pathology 2022;51(12):1235-1239
Objective: To investigate the diagnostic value of expression of CCNB3 and BCOR in BCOR-CCNB3 sarcoma (BCS). Methods: Fifteen cases of BCS confirmed by fluorescence in situ hybridization (FISH) and/or reverse transcription-polymerase chain reaction (RT-PCR) from January 2014 to October 2021 at Beijing Jishuitan Hospital were collected. Immunohistochemical EnVision method was used to detect the expression of CCNB3 and BCOR in 15 cases of BCS and in 65 non-BCS tumors (54 cases of Ewing's sarcoma, 5 cases of CIC rearranged sarcoma, 4 cases of synovial sarcoma, 1 case of mesenchymal chondrosarcoma and 1 case of soft tissue clear cell sarcoma). Results: Immunohistochemical staining for CCNB3 revealed strongly diffuse nuclear staining in 14 of 15 (14/15) BCS cases, whereas none of the 65 non-BCS tumors showed any staining. Immunohistochemical staining for BCOR showed strongly diffuse nuclear staining in 11 (11/14) BCS cases; seven of the 65 (7/65, 10.8%) non-BCS tumors showed variable staining (five cases of Ewing sarcoma, one cases of synovial sarcoma, and one case of mesenchymal chondrosarcoma). The sensitivity and specificity of CCNB3 in diagnosing BCS were 93.3% and 100% and these of BCOR were 78.6% and 89.2%, respectively. Conclusions: CCNB3 is a highly sensitive and specific marker for BCS.The antibody may help screening BCS.
Humans
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Sarcoma, Synovial/genetics*
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In Situ Hybridization, Fluorescence
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Cyclin B/genetics*
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Proto-Oncogene Proteins/genetics*
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Repressor Proteins/genetics*