| 1. |
- Yu, Ling-Zhu, et al.
(författare)
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MEK1/2 regulates microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte meiotic maturation.
- 2007
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Ingår i: Cell cycle (Georgetown, Tex.). - 1551-4005. ; 6:3, s. 330-8
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that MAPK plays pivotal roles in oocyte maturation, but the function of MEK (MAPK kinase) remains unknown. We have studied the expression, subcellular localization and functional roles of MEK during meiotic maturation of mouse oocytes. Firstly, we found that MEK1/2 phoshorylation (p-MEK1/2, indicative of MEK activation) was low in GV (germinal vesicle) stage, increased 2h after GVBD (germinal vesicle breakdown), and reached the maximum at metaphase II. Secondly, we found that P-MEK1/2 was restricted in the GV prior to GVBD. In prometaphase I and metaphase I, P-MEK1/2 was mainly associated with the spindle, especially with the spindle poles. At anaphase I and telophase I, p-MEK1/2 became diffusely distributed in the region between the separating chromosomes, and then became associated with the midbody. The association of p-MEK1/2 with spindle poles was further confirmed by its colocalization with the centrosomal proteins, gamma-tubulin and NuMA. Thirdly, we have investigated the possible functional role of MEK1/2 activation by intravenous administration and intrabursal injection of a specific MEK inhibitor, U0126, and by microinjection of MEK siRNA into oocytes. All these manipulations cause disorganized spindle poles and spindle structure, misaligned chromosomes and larger than normal polar bodies. Our results suggest that MEK1/2 may function as a centrosomal protein and may have roles in microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte maturation.
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| 2. |
- Meng, Wen-Jian, et al.
(författare)
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Microsatellite instability did not predict individual survival in sporadic stage II and III rectal cancer patients
- 2007
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 72:1-2, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients. Copyright © 2007 S. Karger AG.
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| 3. |
- Meng, Wen-Jian, et al.
(författare)
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Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability
- 2007
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Ingår i: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 13:27, s. 3747-3751
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI). Methods: Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used. Results: Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls. Conclusion: Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H. © 2007 WJG. All rights reserved.
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| 4. |
- Xue, Yuan, et al.
(författare)
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FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
- 2008
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Ingår i: Proceedings of The National Academy of Sciences of The United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:29, s. 10167-10172
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Tidskriftsartikel (refereegranskat)abstract
- Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.
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| 5. |
- Xue, Yuan, et al.
(författare)
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Hypoxia-independent angiogenesis in adipose tissues during cold acclimation.
- 2009
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 9:1, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism remain poorly understood. Here, we show that exposure of mice to cold led to activation of angiogenesis in both white and brown adipose tissues. In the inguinal depot, cold exposure resulted in elevated expression levels of brown-fat-associated proteins, including uncoupling protein-1 (UCP1) and PGC-1alpha. Proangiogenic factors such as VEGF were upregulated, and endogenous angiogenesis inhibitors, including thrombospondin, were downregulated. In wild-type mice, the adipose tissues became hypoxic during cold exposure; in UCP1(-/-) mice, hypoxia did not occur, but, remarkably, the augmented angiogenesis was unaltered and was thus hypoxia independent. Intriguingly, VEGFR2 blockage abolished the cold-induced angiogenesis and significantly impaired nonshivering thermogenesis capacity. Unexpectedly, VEGFR1 blockage resulted in the opposite effects: increased adipose vascularity and nonshivering thermogenesis capacity. Our findings have conceptual implications concerning application of angiogenesis modulators for treatment of obesity and metabolic disorders.
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| 6. |
- Xue, Yuan
(författare)
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Mechanism of pathological angiogenesis in adipose tissue and tumor
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis is critical for both malignant diseases, such as cancer, and non-malignant diseases, such as obesity and metabolic disorders. Majority of tissues and organs are highly vascularized. The malfunctions of tissue microenvironment are always accompanied with or dependent on the alterations of vasculature. Therefore, anti-angiogenic agents provide novel therapeutic targets for prevention and treatment of malignant and non-malignant diseases. This thesis presents the identification and further investigation of mechanism of angiogenesis in adipose tissue metabolism and cancer development. Multiple factors spatiotemporally regulate adipogenesis and angiogenesis. In a transgenic mouse model described in the first constituent paper, FOXC2 in the adipose tissue affects angiogenesis, vascular patterning and functions. FOXC2 controls angiopoietin-2 (Ang-2) expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2 specific antagonist L1-10 reverses the vascular alterations. In another physiological model described in the second paper, exposure of mice to cold temperature leads to activation of angiogenesis in both white and brown adipose tissues. Proangiogenic factors, such as VEGF, are upregulated, and endogenous angiogenesis inhibitors, such as thrombospondin, are downregulated during the adipose tissue transformation. Intriguingly, the cold-induced angiogenesis is independent of hypoxia. VEGFR2 blockage abolishes the cold-induced angiogenesis and significantly impairs nonshivering thermogenesis capacity. Unexpectedly, VEGFR1 blockage results in the opposite effects. Therefore, the application of angiogenesis modulators can have conceptual implications for the treatment of obesity and disorders. In the third paper, we show both in vitro and in vivo that PDGF-B markedly induces erythropoietin (EPO) mRNA and protein expression levels by targeting the PDGFR positive stromal compartment. Tumor-produced PDGF-B systemically affects spleen and liver by causing hepato-splenomegaly and extramedullary hematopoiesis. PDGF-B induces erythropoietin and promotes tumor growth by, 1) stimulating tumor angiogenesis and 2) stimulating extramedullary hematopoiesis leading to increased oxygen perfusion. Thus, the EPO signaling pathway may be crucial for the development of anti-PDGF cancer therapy.
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| 7. |
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| 8. |
- Zhu, Li-Hua, et al.
(författare)
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Can Arabidopsis AP1 Gene Shorten the Juvenility of Apple?
- 2009
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Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 829, s. 259-264
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Konferensbidrag (refereegranskat)abstract
- Shortening of the juvenile phase is of great importance for apple breeding. Compared to conventional breeding methods, gene technology is more straightforward in reducing juvenility, as it can directly regulate expression of flowering-time genes. In model plant Arabidopsis, a number of flowering-time genes have been identified and characterised. Some of them have also been isolated from other species. Regulation of these genes has been proved to promote early flowering in a number of plant species. In this study, we have introduced the Arabidopsis APETALA1 (AP1) gene into the apple rootstock M26. The transgenic plants have been grown in the greenhouse for two years; however, no early flowering has been observed, although the AP1 gene is constitutively expressed in the transgenic clones, confirmed by RT-PCR analysis.
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| 9. |
- Zhu, Li-Hua, et al.
(författare)
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Plant Size Control in Apple through Genetic Engineering
- 2009
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Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 839, s. 689-694
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Konferensbidrag (refereegranskat)abstract
- Tree size control is essential for modern apple production. Chemical controls and different managements have been practically used in commercial production of apple rootstocks and cultivars in order to generate dwarf trees. However, these practices are either inefficient or unfriendly to human health and environment. In contrast, genetic engineering offers a better possibility to improve plant properties. By introducing well-characterised genes that control the growth vigour, it is possible to dwarf an existing genotype without disturbing its main genetic background. Up to now, some genes have been introduced into different plant species and proved to be effective in reducing plant size. Among the genes tested, the rolC, gai and GA oxidase have shown to be able to reduce plant size in most cases. In our previous studies, we have introduced the rolC and gai genes into apple rootstocks and cultivars. Both in vitro and grown analysis in greenhouse have shown that transgenic plants with one of these genes did display reduced plant height in most cases. Since plant height is mainly controlled by gibberellins, regulation of GA biosynthesis would be a better way to control plant size in the future.
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