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| 2. |
- Fan, Chuan-Wen, et al.
(författare)
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Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
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| 3. |
- Gao, Jingfang, 1966-, et al.
(författare)
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Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:3, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The inhibitory proteins, IκBs, regulate the activity of nuclear factor kappa-beta (NF-κB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IκBs may be involved in cancer development through the activation of NF-κB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3′ UTR of NFKBIA (encoding IκBα) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. Material and methods. A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism. Results. The frequency of the AG genotype was increased in the Chinese patients ≥50 years of age compared with the Chinese controls (odds ratio (OR) = 3.06, 95% confidence interval (CI) = 1.55-6.02, p=0.001), even when adjusted for age (OR = 3.20, 95% CI = 1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl = 1.28-7.60, p=0.01). Conclusions. Chinese individuals ≥50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. © 2007 Taylor & Francis.
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| 4. |
- Gao, Jingfang, et al.
(författare)
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Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer
- 2009
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Ingår i: DIGESTIVE AND LIVER DISEASE. - : Elsevier BV. - 1590-8658. ; 41:2, s. 116-122
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The aim of this study was to get a deeper understanding into how adults with cerebral palsy (CP) experience physiotherapy and physical activity in a perspective from childhood to adulthood; and how personal and environmental factors influence possibilities for physiotherapy and physical activity. Method. Data was collected through interviews with 22 community-living adults (35-68 years) with CP, from five counties in Sweden. The questions were open-ended and the interviews were taped and transcribed to written language. The material was analysed through qualitative content analysis, a classification process resulting in different themes. Results. The narratives from the 22 informants, based on experiences from childhood to adulthood, resulted in a description of prerequisites for carrying out physiotherapy and physical activity. Five different themes were identified: (i) Being enjoyable, (ii) Giving effects, (iii) Being comprehensible, (iv) Being integrated in daily life, and (v) Supportive healthcare with competent professionals. Conclusion. The information from the interviews elucidates the importance of a lifelong support from healthcare professionals. Physiotherapists with attentiveness to different life situations in combination with good understanding and knowledge in CP could facilitate continuous physical activity in people growing up and ageing with CP.
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| 5. |
- Gao, Jingfang, 1966-, et al.
(författare)
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MANBA polymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:3, s. 372-378
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Tidskriftsartikel (refereegranskat)abstract
- β-mannosidase, encoded by MANBA, has been suggested to be implicated in cancers, while genetic variations in the MANBA in relation to colorectal cancer (CRC) risk has not been examined. In this study, we investigated the relationship of a polymorphic CA repeat in MANBA gene with CRC risk in 152 Swedish CRC patients and 441 Swedish controls, and 196 Chinese CRC patients and 577 Chinese controls, as well as the clinicopathologic significance of this polymorphism on CRC patients, by using capillary electrophoresis. The MANBA genotypes were related to CRC risk in the Swedish population (p=0.03), but not in the Chinese population. In the Swedish population, individuals with < 22 CAs/> 22 CAs had significantly increased risk for CRC compared with those with ≥22 CAs/≥ 22 CAs (gender-age-adjusted analysis: OR 1.93, 95% CI 1.06-3.51). There was no relationship between the polymorphism and clinicopathologic variables. These findings suggest the different susceptibilities of this polymorphism to CRC development in the two populations. © 2008 Taylor & Francis.
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| 6. |
- Gao, Jingfang, et al.
(författare)
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RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer
- 2008
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Ingår i: Histology and Histopathology. - : Histology and Histopathology. - 0213-3911 .- 1699-5848. ; 23:12, s. 1495-1502
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Tidskriftsartikel (refereegranskat)abstract
- RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity. In this study, we immunohistochemically examined MRE11, NBS1 and RAD50 expression in primary CRCs (n = 208), the corresponding distant (n= 41) and adjacent normal mucosa ( n= 130), and lymph node metastases ( n= 26), and investigated their clinicopathological significance in colorectal cancers ( CRCs). We found that the intensity and percentage of MRE11 and NBS1 in primary CRCs were positively correlated with each other and with RAD50 (P < 0.0001). Strong expression of MRE11, NBS1 or combined RAD50/MRE11/NBS1 was related to MSS, positive hMLH1 expression, earlier tumour stage (TNM stage I and II) and favourable survival (P < 0.05). A high percentage of MRE11 expression was associated with less local recurrence and high apoptotic activity (P < 0.05). In MSS CRCs, the expression of MRE11 and NBS1 was stronger than that in normal mucosa (P < 0.05), and strong expression of NBS1 in primary tumour was related to favourable survival of patients in TNM stage I and II (univariate analysis: P = 0.03; multivariate analysis: P = 0.07). In MSI CRCs, neither MRE11 nor NBS1 expression showed differences among normal mucosa, primary tumour and metastasis, or among clinicopathological variables. In conclusion, RAD50/MRE11/NBS1 proteins interacted with each other, which had different clinicopathological significance in MSS and MSI CRCs, and further, each component of the complex might have additional roles. NBS1 might be a prognostic factor for patients with MSS tumour in TNM stage I and II.
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| 7. |
- Gao, Jingfang, et al.
(författare)
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Relationships of tumor inflammatory infiltration and necrosis with microsatellite instability in colorectal cancers
- 2005
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Ingår i: World Journal of Gastroenterology. - 1007-9327. ; 11:14, s. 2179-2183
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The relationships between microsatellite instability (MSI) and survival in colorectal cancer patients are not consistent. The favorable survival of patient with MSI has been suggested to be related to pronounced inflammatory infiltration; however, the reason for non-association of MSI with survival is unclear. Our aims were to investigate the associations of inflammatory infiltration and tumor necrosis (TN) with microsatellite status and clinicopathological factors in colorectal cancer patients in whom MSI was not related to survival. Methods: Three hundred and one colorectal adenocar-cinomas were evaluated for inflammatory infiltration and 300 for TN under light microscope. Results: Low infiltration at invasive margin (c2 = 3.94, P = 0.047) and in whole tumor stroma (c2 = 3.89, P = 0.049) was associated with MSI, but TN was not (c2 = 0.10, P = 0.75). Low infiltration was related to advanced stage (c2 = 8.67, P = 0.03), poorer differentiation (c2 = 8.84, P = 0.03), DNA non-diploid (c2 = 10.04, P = 0.002), higher S-phase fraction (c2 = 11.30, P = 0.004), positive p53 expression (c2 = 7.94, P = 0.01), and worse survival (P = 0.03 for both univariate and multivariate analyses). Abundant TN was related to advanced stage (c2 = 17.74, P = 0.001) and worse survival (P = 0.02 for univariate, and P = 0.05 for multivariate analysis). Conclusion: The result that high inflammatory infiltration was not related to MSI might help explain the non-association of MSI with survival in colorectal cancer patients.
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| 8. |
- Gao, Jingfang, et al.
(författare)
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Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer
- 2004
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 6:6, s. 796-801
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Tidskriftsartikel (refereegranskat)abstract
- Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16-3.37, P = .01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.
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| 9. |
- Gao, Jingfang, et al.
(författare)
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The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers
- 2008
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Ingår i: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; 24:2, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)_{9} at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs {may be a cellular response against tumor from further progression}, while hRAD50 mutation may be involved in the development of MSI CRCs.
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| 10. |
- Lewander, Andreas, et al.
(författare)
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NF-kappa B p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients
- 2012
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 27:4, s. 447-452
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Tidskriftsartikel (refereegranskat)abstract
- The NF-kappa B transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-kappa B p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). The NF-kappa B p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.
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