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  • 1.
    Arbman, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Colorectal cancer in Östergötland: risk factors, diagnosis, and quality of treatment1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this investigation colorectal cancer in the county of Östergötland has been studied with emphasis on risk factors, diagnostic efforts, and the results of treatment.

    In two case-control studies on food and colorectal cancer, a decreased risk was associated with a high intake of cereal fibre, total fibre, and calcium per unit energy consumed as well as a high intake of raw vegetables. Processed meat was associated with an increased lisk for colon cancer and alcohol with an increased risk for rectal cancer. Drug consumption was also found to influence the cancer risk.

    In a case-control study on occupational factors and the risk for colorectal cancer, some occupations seemed to influence the risk for colon and rectal cancer in different ways. Twenty years of physically active work significantly decreased the risk for left-sided colon cancer but increased the risk for rectal cancer. Accordingly, twenty year of sedentary work significantly decreased the risk for rectal cancer.

    Known risk factors were found in 12% of colorectal cancer patients, though previous cholecystectomy did not turn out to be a risk factor.

    The symptoms of colon cancer are vague and unspecific, whereas bleeding is prominent and a dominating symptom in rectal cancer. Conflicting results have been presented regarding the importance of a short delay between onset of symptoms and treatment. In our study, a more favourable stage distribution was found for rectal cancer with a very short delay between start of symptoms and treatment, but not for colon cancer.

    Results of treatment for colorectal cancer show considerable variation in different series, which can be due to differences in selection and classification as well as in treatment. A computerized system for quality assurance of colorectal cancer was introduced in Östergötland in 1984. All cases diagnosed 1984-1986 were registered in this system, making it possible to study outcome of treatment for an unselected population. The results of treatment in terms of postoperative mortality and five year survival were comparable to the results from specialised international centres, but local recunence rate after operation for rectal cancer was high (20%).

    To reduce this local recurrence rate, the technique of total mesorectal excision was introduced in three of the surgical departments in the county. Using the system for quality assurance, the local recunence rate during a three year period before the change in technique was compared with a three year period when the new technique was used. The local recunence rate was significantly reduced in the later period without any change in postoperative complications.

    In conclusion this study shows an environmental influence on cancer-risk that may be different for colon and rectal cancer. The usefulness of a continuous quality assurance system to detect shmtcomings in diagnosis and treatment and to evaluate new techniques is also shown. Finally, total mesorectal excision reduces the local recurrence rate for rectal cancer in an unselected population treated in different kinds of hospital.

  • 2.
    Arbman, Gunnar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Påhlman, Lars
    Uppsala University, Sweden.
    Glimelius, Bengt
    Uppsala University, Sweden / Karolinska Institutet, Stockholm, Sweden.
    The rise and fall of a longed for clinical trial in patients with generalized colorectal cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, p. 1779-1782Article in journal (Other academic)
  • 3. Emterling, A
    et al.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer2004In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 15, no 2, p. 242-246Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. Patients and methods: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. Results: MSI (13% of 438 cases) was not associated with survival (rate ratio=0.97, 95% confidence interval =0.57-1.64, P=0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P=0.01) and negative/weak expression of hMLH1 (P=0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P=0.01), proximal tumour (P=0.01), stage B (P=0.01) and poor differentiation (P=0.047). Conclusions: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.

  • 4.
    Emterling, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Skoglund, Johanna
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Schneider, José
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Evertsson, Sofia
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Clinicopathological significance of Nup88 expression in patients with colorectal cancer2003In: Oncology, ISSN 0890-9091, Vol. 64, no 4, p. 361-369Article in journal (Refereed)
    Abstract [en]

    Objective: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors.

    Materials and Methods: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases.

    Results: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02).

    Conclusions: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.

  • 5.
    Evertsson, Sofia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wallin, Åsa
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Rütten, Sabine
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Emterling, Anna
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Microsatellite instability and MBD4 mutation in unselected colorectal cancer2003In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 23, no 4, p. 3569-3574Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.

    PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.

    RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.

    CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.

  • 6.
    Gao, Jingfang
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology .
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    He, L..
    Zhang, Zhiyong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology .
    Zhao, Z.
    Rosell, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    MANBA polymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 3, p. 372-378Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Rearden, Ann
    Department of Pathology, University of California-San Diego, La Jolla, CA, USA.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer2004In: Neoplasia, ISSN 1522-8002, Vol. 6, no 6, p. 796-801Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Wadhra, Tabasum Imran
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Relationships of tumor inflammatory infiltration and necrosis with microsatellite instability in colorectal cancers2005In: World Journal of Gastroenterology, ISSN 1007-9327, Vol. 11, no 14, p. 2179-2183Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Knutsen Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Franlund, B
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer2009In: DIGESTIVE AND LIVER DISEASE, ISSN 1590-8658, Vol. 41, no 2, p. 116-122Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Gao, Jingfang
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Pfeifer, Daniella
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    He, Lu-Jun
    Qiao, Fang
    Zhang, Zhiyong
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wang, Zhen-Lei
    Jia, Cun-Rong
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 3, p. 345-350Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Division of Biomedicine, School of Life Science, Skövde University, Skövde, Sweden.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, p. 1495-1502Article in journal (Refereed)
    Abstract [en]

    RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity. In this study, we immunohisto-chemically 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 clinicopathlogical 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.

  • 12.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers2008In: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 24, no 2, p. 127-134Article in journal (Refereed)
    Abstract [en]

    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.

  • 13.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Shen, Yang Mei
    Sichuan University, China.
    Wang, Chao-Jie
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Skövde University, Sweden.
    Stratmann, Johannes
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery VHN.
    Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines2012In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 10, no 109Article in journal (Refereed)
    Abstract [en]

    Background: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. less thanbrgreater than less thanbrgreater thanMaterial and methods: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. less thanbrgreater than less thanbrgreater thanResults: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/- 0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p andlt; 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p andlt; 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-kappa B, p73, Rad50 and apoptosis (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-kappa B signaling pathway.

  • 14.
    Hjalmarsson, Claes
    et al.
    Kalmar Hospital, Sweden; Halland Hospital, Sweden.
    Karlberg, Jonas
    Halland Hospital, Sweden.
    Tornqvist, Pelle
    Halland Hospital, Sweden.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Frisk, Bjorn
    Skaraborg Hospital, Sweden.
    Modin, Marina
    Skaraborg Hospital, Sweden.
    Orally Administered Trimethoprim-Sulfamethoxazole and Metronidazole as Infection Prophylaxis in Elective Colorectal Surgery2015In: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 16, no 5, p. 604-610Article in journal (Refereed)
    Abstract [en]

    Background: This randomized clinical trial evaluated orally administered trimethoprim-sulfamethoxazole and metronidazole (TSM) in elective colorectal surgery as prophylactic for post-operative surgical site infections (SSI). Methods: Patients undergoing elective colorectal resection were evaluated for inclusion. Randomized subjects received either orally administered TSM or intravenously administered cefuroxime and metronidazole (control group, CXM). The primary endpoint was the rate of SSI. Results: A total of 1073 subjects were randomized to either control (540) or TSM (533). 486 patients in the TSM group and 499 in the control group were followed-up with after 4 weeks. Thirty-seven (3.8%) patients were afflicted by SSI at discharge from hospital and 69 (7.0%) at follow-up four weeks after surgery. After four weeks, the rate of incisional SSI was 7.0% in the TSM group and 3.6% in the control group (p=0.022). For organ/space SSI and the other complications monitored in the study, no differences were observed between the groups. Conclusion: Orally administered TSM as prophylaxis before elective colorectal surgery results in a low rate of organ/space SSI but an increased rate of incisional SSI compared with intravenously administered cefuroxime and metronidazole. Thus, when considering orally administered TSM, because of environmental concerns or for economic reasons, the slightly increased infection rate has to be kept in mind.

  • 15.
    Jansson, Agneta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    mRNA and protein expression of PUMA in sporadic colorectal cancer.2004In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 12, no 6, p. 1245-1249Article in journal (Refereed)
    Abstract [en]

    PUMA is a BH3-only member of the Bcl-2 family, up-regulated by p53 as a response to DNA damage. We have investigated the mRNA expression of PUMA with real-time PCR in 94 colorectal adenocarcinomas and the corresponding normal mucosa. Among them PUMA protein expression was investigated with immunohistochemistry in 23 tumours and 17 corresponding normal mucosa samples. The mRNA expression of PUMA decreased in 4% and increased in 4% of the tumours compared with the normal mucosa. The protein expression of PUMA decreased in 6% and increased in 29% of the tumours compared with the normal mucosa. Decreased PUMA expression in the tumour compared with the corresponding mucosa was correlated with the distal colon and rectum (P=0.02). We did not find any other relationship to clinical or pathological features. We suggest that the changes in PUMA expression may be of minor importance in the development of colorectal cancer.

  • 16.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital Hospital, Norrköping, Sweden.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer2003In: International Journal of Oncology, ISSN 1019-6439, Vol. 22, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins.

  • 17.
    Jansson, Agneta K.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Emterling, Anna M.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    The BH3-only member Noxa may not be involved in the development of unselected colorectal cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Noxa is an BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Further, we searched for mutations in the Noxa gene using single stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumours and decreased in 9% and increased in 16% of the tumours compared to the normal mucosa, but these changes did not have any clinical or pathological significance. We did not find any mutations in the gene. Thus, our observations suggest that the variations in Noxa gene may not be of particular importance in the development of unselected colorectal cancer.

  • 18.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    NF-κB p65 phosphorylated at Serine-536 is an independent prognostic factor in Swedish colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: NF-κB transcription factor protein family has diverse cellular and biological functions, and post-translational modification is important to regulate these functions. An important site of phosphorylation of 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 a phospho-Ser536-p65 in colorectal cancers and its relationship to clinicopathological factors of the patients.

    Materials and Methods: Expression of phospho-Ser536-p65 was examined by using immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens and 18 metastases in the lymph nodes.

    Results: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumour (p<0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumours correlated with worse survival of the patients independent of gender, age, tumor location, stage and differentiation (p=0.04, hazard ratio 1.89, 95% CI 1.03-3.47).

    Conclusion: The NF-κB p65 subunit phosphorylated at Serine-536 is anindependent prognostic factor in colorectal cancer patients.

  • 19.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery VHN.
    Zhang, Hong
    University of Skövde.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    NF-kappa B p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients2012In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 27, no 4, p. 447-452Article in journal (Refereed)
    Abstract [en]

    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. less thanbrgreater than less thanbrgreater thanIn 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. less thanbrgreater than less thanbrgreater thanThe expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p andlt; 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). less thanbrgreater than less thanbrgreater thanThe NF-kappa B p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.

  • 20.
    Loftås, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Fomichov Casaballe, Victoria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer2016In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 6, p. 801-807Article in journal (Refereed)
    Abstract [en]

    Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

  • 21.
    Meng, Wen-Jian
    et al.
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Ma, Qin
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 32Article in journal (Refereed)
    Abstract [en]

    The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

  • 22.
    Moparhti, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Kayed, Hany
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Kleeff, Jörg
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Zentgraf, Hanswalter
    Applied Tumor Virology, University of Heidelberg, Heidelberg, Germany.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 30, no 1, p. 91-95Article in journal (Refereed)
    Abstract [en]

    MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.

  • 23.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Polymorphism of the p73 gene in relation to colorectal cancer risk and survival2005In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 26, no 1, p. 103-107Article in journal (Refereed)
    Abstract [en]

    The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer risk are inconsistent, and the significance of loss of heterozygosity (LOH) of the gene is unclear. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. 179 patients with colorectal cancer and 260 healthy controls were genotyped for the polymorphism by PCR-restriction fragment length polymorphism (RFLP). Fifty informative cases were examined for LOH in tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n = 12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2% in controls, respectively. The frequencies of the genotypes in the patients and controls were significantly different (P = 0.02). The patients carrying the AT allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95% CI = 1.15-5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but was not significantly changed between primary tumours and metastases (P = 1.0). In conclusion, the AT/AT homozygotes may have a greater risk of developing colorectal cancer, while the patients who carried the AT allele had a better prognosis.

  • 24.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

  • 25.
    Shen, Yang-mei
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Olsson, Birgit
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis2011In: International Journal of Biological Markers, ISSN 0393-6155, E-ISSN 1724-6008, Vol. 26, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    Background: To investigate the expression of glucose transporter 1 (GLUT1) in colorectal cancer (CRC) and its relationship to clinicopathological variables. Methods: The expression of GLUT1 in 163 primary tumors together with the corresponding normal mucosa, and 36 liver metastases was examined using real-time PCR. Results: The mean value of GLUT1 was higher in primary tumors (50.390 +/- 68.648) than in the corresponding normal mucosa (20.437 +/- 28.703, p less than 0.0001), while there was no significant difference in GLUT1 expression between CRC and liver metastasis (50.390 +/- 68.648 vs 52.277 +/- 52.482, p = 0.190). In CRCs, GLUT1 expression was higher in poorly differentiated than in well and moderately differentiated tumors (p = 0.022), and higher in stage III + IV than in stage I + II tumors (p = 0.035). The patients with high-expressed GLUT1 had a worse prognosis than those with low-expressed GLUT1 independently of gender, age, tumor site, stage and differentiation (p = 0.026, RR 2.737, 95% CI 1.126-6.651) in stage I-III CRCs. In liver metastasis, GLUT1 expression was higher in larger tumors than in smaller ones (p = 0.025). Conclusions: Overexpression of GLUT1 in stage I-III CRCs was independently associated with poor prognosis.

  • 26.
    Shen, Yang-mei
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Wei, Yu-Quan
    Sichuan University.
    Zhang, Hong
    University of Skövde.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Olsson, Birgit
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Peng, Feng
    Sichuan University.
    Yang, Han-Shuo
    Sichuan University.
    Wang, Chun-Ting
    Sichuan University.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Novel gene hBiot2 is an independent prognostic factor in colorectal cancer patients2012In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 27, no 2, p. 376-382Article in journal (Refereed)
    Abstract [en]

    The present study investigated the expression of the novel gene hBiot2 in colorectal cancer (CRC) and its relationships with clinicopathological variables in CRC patients. The expression of hBiot2 in 163 primary CRCs together with the corresponding normal mucosa, 36 liver metastases and 5 colon cancer cell lines was examined using real-time PCR. In situ hybridization (ISH) was performed to evaluate the localization of hBiot2 expression in CRC and normal mucosa. hBiot2 expression at the RNA level was localized in the nucleus of tumor cells and normal epithelial cells. The mean expression of hBiot2 in the CRCs (243.571 +/- 564.569) was higher compared to the normal mucosa (107.252 +/- 413.635, Pandlt;0.0001) and liver metastasis samples (42.002 +/- 40.809, P=0.0002). hBiot2 expression was increased from stages I + II to III (P=0.047), and no difference in the expression was found in stages III and IV (P=0.452). A high value of hBiot2 was associated with a poorer prognosis compared with a low value independently of gender, age, tumor site, stage and differentiation (P=0.007, RR 7.519, 95% Cl 1.729-32.704). Liver metastasis, smaller tumors, non-local recurrence and primary liver surgery alone were associated with a higher value of hBiot2 compared to larger tumors, local recurrence and repeated liver surgery (P=0.003, 0.044 and 0.026, respectively). An inverse relationship was found between hBiot2 expression and the metastatic potential of the colon cancer cell lines. Thus, increased expression of hBiot2 may be an early and interim event in the development of CRC. A higher expression of hBiot2 in primary CRC patients independently indicates a poorer prognosis.

  • 27. Skoglund, Johanna
    et al.
    Emterling, Anna
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Anglard, Patrick
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Clinicopathological significance of stromelysin-3 expression in colorectal cancer2004In: Oncology, ISSN 0890-9091, Vol. 67, no 1, p. 67-72Article in journal (Refereed)
    Abstract [en]

    Objective: Stromelysin-3 (ST3) is a member of the matrix metalloproteinases and suggested to play a role in tissue remodeling observed in growth and metastasis of tumors. ST3 overexpression in breast cancer is associated with a worse outcome. Our aims were to analyze ST3 expression in primary colorectal tumors and metastases, and further to identify relationships of the expression to clinicopathological factors. Materials and Methods: ST3 expression was immunohistochemically analyzed in 200 primary colorectal adenocarcinomas and 36 corresponding lymph node metastases. Results: Scoring was performed by counting the percentages of positive cells and the percentages of positive areas. One hundred and one (51%) cases showed ≤5% positive cells and 99 (49%) >5% positive cells. One hundred and two (51%) cases showed ≤30% positive area and 98 (49%) >30% positive area. ST3 expression determined by both scoring methods was individually related to females, distally located tumors, infiltrative growth pattern and microsatellite stability. No relationship was found with age, Dukes' stage, differentiation and survival. Conclusions: These results suggest that ST3 protein was more involved in the pathway of colorectal cancer development in females, distal locations, infiltrative growth patterns and microsatellite stability. Copyright © 2004 S. Karger AG, Basel.

  • 28.
    Sun, Xiao-Feng
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Asklid, Daniel
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival2005In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 11, no 43, p. 6875-6879Article in journal (Refereed)
    Abstract [en]

    Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

  • 29.
    Wang, Chao-Jie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Frånbergh-Karlson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Wang, Da-Wei
    The Third Hospital of Hebei Medical University, China.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Zhang, Hong
    Örebro University, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Clinicopathological significance of BTF3 expression in colorectal cancer2013In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 34, no 4, p. 2141-2146Article in journal (Refereed)
    Abstract [en]

    Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription factor and is also involved in apoptosis regulation. Increasing evidence shows that BTF3 is aberrantly expressed in several kinds of malignancies, but there is no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n  = 35), and analyzed its relationships with clinicopathological and biological variables. Our results showed that BTF3 staining significantly increased from distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p = 0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a higher expression than those with worse differentiation (56 % vs. 37 %, p  = 0.031). There were positive correlations of BTF3 expression with nuclear factor kappa B (NF-κB), RAD50, MRE11, NBS1, and AEG-1 (p  < 0.05). In conclusion, BTF3 overexpression may be an early event in CRC development and could be useful biomarker for the early stage of CRCs. BTF3 has positive correlations with NF-κB, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways in CRC.

  • 30.
    Wang, Mo-Jin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Nodin, Bjorn
    Lund University, Sweden.
    Meng, Wen-Jian
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Wang, Cun
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 10645Article in journal (Refereed)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

  • 31.
    Wang, Mo-Jin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Zhang, Hong
    University of Örebro, Sweden.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 51, p. e2350-Article in journal (Refereed)
    Abstract [en]

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P &lt; 0.001) and LC (46.9% vs 27.7%, P &lt; 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P &lt; 0.001; LC, P = 0.026), prominently in stage III (SEER, P &lt; 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P &lt; 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

  • 32.
    Yang, Lie
    et al.
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Ma, Qin
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Yu, Yong-Yang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Wang, Cun
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Meng, Wen-Jian
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Jarlsfelt, Ingvar
    Jonköping Hospital, Sweden.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer A STROBE-compliant article2014In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 93, no 28Article in journal (Refereed)
    Abstract [en]

    The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age greater than= 70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/ radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged less than70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged greater than= 80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged less than70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged greater than= 80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged greater than= 80 years had a higher 30-day mortality than younger patients (odds ratio OR], 2.37; 95% confidence interval CI], 1.6-4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.052.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged greater than= 80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.

  • 33.
    Zhou, Jin
    et al.
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Yang, Lie
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Li, Yuan
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Chen, Ke-Ling
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Zhou, Bin
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Yu, Yong-Yang
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Wang, Cun
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Mo, Xian-Ming
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Lu, You
    Sichuan University, Peoples R China .
    Zhou, Zong-Guang
    Sichuan University, Peoples R China Sichuan University, Peoples R China .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The prognostic significance of peroxisome proliferator-activated receptor beta expression in the vascular endothelial cells of colorectal cancer2014In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 49, no 3, p. 436-445Article in journal (Refereed)
    Abstract [en]

    Currently, little is known regarding the role of peroxisome proliferator-activated receptor-beta (PPAR beta) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR beta expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients. The expression and localization of PPAR beta in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients. PPAR beta was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR beta in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR beta in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR beta in CRC cells but increased expression in VECs exhibited less favorable prognosis. PPAR beta might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs.

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