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  • 651. Zeleniuch-Jacquotte, Anne
    et al.
    Lundin, Eva
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Micheli, Andrea
    Koenig, Karen L
    Lenner, Per
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Muti, Paola
    Shore, Roy E
    Johansson, Ingegerd
    Umeå universitet, Medicinsk fakultet, Odontologi, Kariologi.
    Krogh, Vittorio
    Lukanova, Annekatrin
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Afanasyeva, Yelena
    Rinaldi, Sabina
    Arslan, Alan A
    Kaaks, Rudolf
    Berrino, Franco
    Hallmans, Göran
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Näringsforskning.
    Toniolo, Paolo
    Adlercreutz, Herman
    Circulating enterolactone and risk of endometrial cancer2006Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, nr 10, s. 2376-2381Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

  • 652. Zhang, Lu
    et al.
    Hu, Jin
    Zirakzadeh, Ali A .
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Medicine, Immunology and Allergy Unit, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Rosvall, Jesper
    Hedlund, Mats
    Hu, Ping Sheng
    P A Wallin, Robert
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Detection of micro-metastases by flow cytometry in lymph nodes from patients with penile cancer2018Inngår i: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 18, nr 1, artikkel-id 86Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The tumor draining lymph node concept was first described in penile cancer for staging. Immunohistochemistry and histopathology evaluations are routinely used in clinical practice to examine lymph nodes for metastasis. However, these methods are time-consuming with low diagnostic accuracy and micro-metastases might be missed. In this study, we aim to evaluate detection of metastatic cells in draining lymph nodes by flow cytometry.

    METHODS: To assess the sensitivity of micro-metastasis detection by FACS (Fluorescence-activated cell sorting), HeLa cells were titrated into Peripheral blood mononuclear cells (PBMCs) and expression of pan-cytokeratin AE1/AE3 was analyzed. Single cell suspensions were separately prepared from 10 regional lymph nodes obtained from 5 patients with invasive penile cancer undergoing radical surgery and lymph node dissection. Lymph node dereived cells were examined for cell surface expression of EpCAM, E-cadherin and intracellular expression of pan-cytokeratin AE1/AE3 by FACS.

    RESULTS: Ten lymph nodes from 5 penile cancer patients were investigated in a head-to-head comparison between FACS and pathology examination of sections. All metastatic lymph nodes verified by pathology examination were also identified by FACS. Two additional lymph nodes with micro-metastases were diagnosed by FACS only.

    CONCLUSIONS: FACS analyses of pan-cytokeratin AE1/AE3 stained single cells from tumor draining lymph nodes can be used to detect micro-metastases in patients with penile cancer patients.

  • 653. Zhang, Lu
    et al.
    Hu, Jin
    Zirakzadeh, Ali
    Rosvall, Jesper
    Hedlund, Mats
    Hu, Pingsheng
    Wallin, Robert
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Immune responses against Human Papilloma virus in draining lymph nodes from patients with penile cancer2017Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, nr 4, s. 339-339Artikkel i tidsskrift (Annet vitenskapelig)
  • 654. Zhao, Hongjuan
    et al.
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Grankvist, Kjell
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Rasmuson, Torgny
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Tibshirani, Robert
    Brooks, James D
    Gene expression profiling predicts survival in conventional renal cell carcinoma2006Inngår i: PLoS Med, ISSN 1549-1676, Vol. 3, nr 1, s. e13-Artikkel i tidsskrift (Fagfellevurdert)
  • 655. Zhao, Hongjuan
    et al.
    Zongming Ma,
    Tibshirani, Robert
    Higgins, John P T
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Brooks, James D
    Alteration of gene expression signatures of cortical differentiation and wound response in lethal clear cell renal cell carcinomas.2009Inngår i: PloS one, ISSN 1932-6203, Vol. 4, nr 6, s. e6039-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clear cell renal cell carcinoma (ccRCC) is the most common malignancy of the adult kidney and displays heterogeneity in clinical outcomes. Through comprehensive gene expression profiling, we have identified previously a set of transcripts that predict survival following nephrectomy independent of tumor stage, grade, and performance status. These transcripts, designated as the SPC (supervised principal components) gene set, show no apparent biological or genetic features that provide insight into renal carcinogenesis or tumor progression. We explored the relationship of this gene list to a set of genes expressed in different anatomical segments of the normal kidney including the cortex (cortex gene set) and the glomerulus (glomerulus gene set), and a gene set expressed after serum stimulation of quiescent fibroblasts (the core serum response or CSR gene set). Interestingly, the normal cortex, glomerulus (part of the normal renal cortex), and CSR gene sets captured more than 1/5 of the genes in the highly prognostic SPC gene set. Based on gene expression patterns alone, the SPC gene set could be used to sort samples from normal adult kidneys by the anatomical regions from which they were dissected. Tumors whose gene expression profiles most resembled the normal renal cortex or glomerulus showed better survival than those that did not, and those with expression features more similar to CSR showed poorer survival. While the cortex, glomerulus, and CSR signatures predicted survival independent of traditional clinical parameters, they were not independent of the SPC gene list. Our findings suggest that critical biological features of lethal ccRCC include loss of normal cortical differentiation and activation of programs associated with wound healing.

  • 656. Zheng, S Lilly
    et al.
    Sun, Jielin
    Wiklund, Fredrik
    Smith, Shelly
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Li, Ge
    Adami, Hans-Olov
    Hsu, Fang-Chi
    Zhu, Yi
    Bälter, Katarina
    Kader, A Karim
    Turner, Aubrey R
    Liu, Wennuan
    Bleecker, Eugene R
    Meyers, Deborah A
    Duggan, David
    Carpten, John D
    Chang, Bao-Li
    Isaacs, William B
    Xu, Jianfeng
    Grönberg, Henrik
    Cumulative association of five genetic variants with prostate cancer.2008Inngår i: N Engl J Med, ISSN 1533-4406, Vol. 358, nr 9, s. 910-9Artikkel i tidsskrift (Fagfellevurdert)
  • 657. Zirakzadeh, A Ali
    et al.
    Kinn, Johan
    Krantz, David
    Rosenblatt, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
    Winerdal, Malin E
    Hu, Jin
    Hartana, Ciputra Adijaya
    Lundgren, Christian
    Bergman, Emma Ahlén
    Johansson, Markus
    Holmström, Benny
    Hansson, Johan
    Sidikii, Alexander
    Vasko, Janos
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Marits, Per
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer2017Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, s. 63-70Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-α. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

  • 658. Zirakzadeh, A. Ali
    et al.
    Marits, Per
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies2013Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 190, nr 11, s. 5847-5855Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    B lymphocytes contribute to immune surveillance, by tumor-specific Abs and Ag presentation to T lymphocytes, but are insufficiently studied in humans. In this article, we report a flow cytometric investigation of B lymphocyte subpopulations in blood, lymph nodes (LNs), and malignant tissues from 20 patients operated on because of advanced solid tumors. The CD19(+) compartment in peripheral blood was essentially unaltered in patients, as compared with healthy control subjects. In metastatic LNs, signs of B lymphocyte activation were observed, as evidenced by increased proportions of plasmablasts and CD86-expressing cells. In tumor-infiltrating B lymphocytes (TIL-B), both switched memory cells and plasmablasts were expanded, as compared with nonmalignant epithelium. Moreover, pronounced skewing of Ig lambda/Ig kappa ratio was evident among TIL-Bs. By spectratype analysis on IgH, we confirmed a monoclonal expansion of the Vh7 family in TIL-B, also present in a tumor-associated LN. Sequencing the clonally expanded Vh7 revealed signs of somatic hypermutation. In conclusion, B lymphocytes in cancer patients exhibit signs of activation in tumor-associated tissues, likely induced by recognition of tumor Ags. Increased numbers of switched memory cells and plasmablasts in combination with clonal expansion and signs of somatic hypermutation suggest a CD4(+) T lymphocyte-dependent antitumoral response, which may be exploited for immunotherapy.

  • 659.
    Zirakzadeh, Ali A .
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Medicine Solna, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Rosenblatt, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ahlén Bergman, Emma
    Winerdal, Max
    Yang, David
    Cederwall, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Jakobsson, Vivianne
    Hyllienmark, Martin
    Winqvist, Ola
    Marits, Per
    Tumour-associated B cells in urothelial urinary bladder cancer2019Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, artikkel-id e12830Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tumour infiltrating B cells and CD38+ plasma cells have been correlated with survival in different malignancies but their role in urinary bladder cancer is unclear. IL-10 is a multifunctional cytokine with both anti-inflammatory and immunostimulatory properties, that can be released by regulatory B cells (Bregs). We have stained paraffin-embedded tumour sections from 31 patients with invasive urothelial urinary bladder cancer with respect to CD20+ B cells, CD38+ cells, IL-10-expressing cells, IgG, C1q and C3a and analysed the impact of these markers on survival. Interestingly, we observe tumour-associated CD20+ B cells forming follicle-like structures in tumours of some patients. We demonstrate that follicle-like structures, tumour-associated CD38+ cells, IL-10 produced by non-B cells, tumour infiltrating IgG and activation of the complement system, may associate to longer survival of urinary bladder cancer patients. IL-10 expression by tumour-associated Bregs may instead negatively affect prognosis. More research is needed to fully understand the role of B cells and IL-10 in urinary bladder cancer.

  • 660.
    Åstrand, Anders
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Andersson, Britt
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Börje, Ljungberg
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Anders, Bergh
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lindahl, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Prostate cancer detection with a tactile resonance sensor: measurement considerations and clinical setup2017Inngår i: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 17, nr 11, artikkel-id 2453Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (p < 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.

  • 661.
    Åstrand, Anders
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Andersson, Britt M
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jalkanen, Ville
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The first study on whole human prostate ex vivo using a tactile resonance sensor for cancer detectionArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Prostate cancer (PCa) is the most common form of cancer among males in Europe and the USA. A prostatectomy i.e. the removal of the prostate is the most common form of curative treatment. Prostate cancer can be suspected by a blood test for a prostate specific antigen (PSA) and a digital rectal examination (DRE) where a physician palpates the prostate through the rectum and where stiff nodules on the prostate is an indication for PCa. The final diagnosis of PCa is made by microscopic evaluation of ultrasound-guided biopsies taken from suspicious parts of the gland. After a prostatectomy the entire prostate is histopathologically analysed. One area of interest is the superficial part of the prostate gland as tumour growth on the surface suggests that the cancer has spread to other parts of the body.

     

    Tactile resonance sensors can be used to detect areas of different stiffness in soft tissue through a stiffness parameter. It is suggested that tactile resonance sensors can be used to detect prostate cancer since tumours in the human prostate usually is stiffer compared to surrounding healthy glandular tissue.

     

    The aim of the study was to detect tumours on, and beneath the surface, of whole human prostate glands ex vivo using a tactile resonance sensor system (TRSS). Model studies on spherical shaped tissue phantoms made of silicone and porcine tissue were performed to evaluate the ability of the TRSS to detect stiffer volumes at a distance beneath the surface. Finally two resected human prostate glands ex vivo from patients undergoing surgery for prostate cancer were studied.

     

    From the results it was concluded that the clamping force from the rotatable sample holder did not affect the magnitude of the stiffness parameter for the silicone samples. For the porcine muscle samples, the stiffness parameter showed to be affected by clamping forces larger than about 800 mN. The embedded stiff silicone nodules placed about 4 mm under the surface could be detected in both the silicone and biological tissue models with a sensor indentation distance of 0.6 mm. The measurements on resected whole human prostates showed that areas with elevated stiffness parameter values correlated (p < 0.05) with areas where cancer tumours were detected using histolopathological evaluation of the prostate. The tumours were significantly stiffer than the healthy tissue in the dorsal region. This is promising for the development of a clinically useful instrument to detect superficial prostate cancer.

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