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Sökning: WFRF:(Kannisto Päivi)

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1.
  • Arildsen, Nicolai Skovbjerg, et al. (författare)
  • Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method
  • 2019
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 9:1, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • High-grade serous ovarian cancer (HGSOC) is the most common subtype of epithelial ovarian cancer and early detection is challenging. TP53 mutations are a hallmark of HGSOC and detection of these mutations in liquid-based Pap samples could provide a method for early diagnosis. Here we evaluate the use of IBSAFE, an ultra-sensitive droplet digital PCR (ddPCR) method, for detecting TP53 mutations in liquid-based Pap samples collected from fifteen women at the time of diagnosis (diagnostic samples) and/or up to seven years prior to diagnosis (archival samples). We analysed tumours for somatic TP53 mutations with next generation sequencing and were able to detect the corresponding mutations in diagnostic samples from six of eight women, while one patient harboured a germline mutation. We further detected a mutation in an archival sample obtained 20 months prior to the ovarian cancer diagnosis. The custom designed IBSAFE assays detected minor allele frequencies (MAFs) with very high assay sensitivity (MAF = 0.0068%) and were successful despite low DNA abundance (0.17-206.14 ng, median: 17.27 ng). These results provide support for further evaluation of archival liquid-based Pap samples for diagnostic purposes and demonstrate that ultra-sensitive ddPCR should be evaluated for ovarian cancer screening in high-risk groups or in the recurrent setting.
2.
  • Bjurberg, Maria, et al. (författare)
  • Cervixcancer en klinisk utmaning
  • 2015
  • Ingår i: Lakartidningen. - Swedish Medical Association. - 1652-7518. ; 112
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Cervical cancer is the third most common female cancer world wide. In Sweden, some 450 cases are diagnosed annually. One out of three affected Swedish women is under the age of 40. Survival for all stages is 73 % in Sweden. Human papilloma virus (HPV) can be detected in the majority of all cervical cancers. Treatment consists of surgery for early stages, and a combination of chemoradiation and brachytherapy for locally advanced disease. For metastatic disease, the treatment is palliative. Late side effects after treatment may have serious impact on the quality of life. There is a strong need for more efficient treatment of metastatic disease. Current lines of research include surgical strategies, optimised radiotherapy, neoadjuvant therapy, targeted therapy, and immunotherapy including therapeutic vaccines.
3.
  • Buchan, Sarah L., et al. (författare)
  • Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function
  • 2018
  • Ingår i: Immunity. - Cell Press. - 1074-7613. ; 49:5, s. 958-970
  • Tidskriftsartikel (refereegranskat)abstract
    • The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB. Intra-tumoral Treg cells were preferentially depleted by anti-4-1BB mAbs in vivo. Anti-4-1BB mAbs also promoted effector T cell agonism to promote tumor rejection. These distinct mechanisms were competitive and dependent on antibody isotype and FcγR availability. Administration of anti-4-1BB IgG2a, which preferentially depletes Treg cells, followed by either agonistic anti-4-1BB IgG1 or anti-PD-1 mAb augmented anti-tumor responses in multiple solid tumor models. An antibody engineered to optimize both FcγR-dependent Treg cell depleting capacity and FcγR-independent agonism delivered enhanced anti-tumor therapy. These insights into the effector mechanisms of anti-4-1BB mAbs lay the groundwork for translation into the clinic.
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4.
  • Chang, Jing-Yu, et al. (författare)
  • Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation
  • 1989
  • Ingår i: Brain Research. - Elsevier. - 1872-6240. ; 492:1-2, s. 79-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunohistochemistry as well as in vitro uptake and release of [3H]5-HT were performed on pial arteries of rat to investigate the nature of 5-HT containing nerve fibers. Immunoreactive fibers were constantly found only in the basilar, vertebral and superior cerebellar arteries, while in the other parts of the circle of Willis, 5-HT immunofluorescent fibers were absent. After systemic treatment with tryptophan following inhibition of monoamine oxidase with nialamide the immunofluorescence intensity was markedly enhanced. The 5-HT immunoreactive fibers disappeared after superior cervical ganglionectomy or intraventricular administration of 6-hydroxydopamine, but persisted after administration of 5,6-dihydroxytryptamine. When isolated vessels were incubated in low concentration of 5-HT (1 nM) together with nialamide, a very dense plexus of 5-HT immunoreactive fibers appeared in all branches of the circle of Willis. Uptake and release experiments were carried out by incubation of arterial preparations with 3 nM [3H]5-HT (together with nialamide), followed by electrical field stimulation, or by exposure to tyramine or 124 mM potassium, all of which induced a 100%-350% increase in the tritium release over prestimulation values. Preincubation with cocaine and bilateral superior cervical ganglionectomy abolished or markedly attenuated the release upon all modes of stimulation. The results suggested that the 5-HT observed by immunohistochemistry in pial arteries is located in sympathetic nerve terminals where it may serve as a neuromodulator that is released during nerve activation.
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5.
  • Christoffersson, Magnus, et al. (författare)
  • Shoulder dystocia and brachial plexus injury: a case-control study
  • 2003
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - Wiley-Blackwell. - 1600-0412. ; 82:2, s. 147-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective and Background. To evaluate risk factors for shoulder dystocia and brachial plexus injury using a case-control study at the departments of obstetrics and gynecology at the four largest hospitals in southern Sweden. All cases of shoulder dystocia between 1987 and 1993 inclusive were identified. For each case, two control infants with similar birthweight (+/- 100 g) and identical year of birth were randomly selected. Methods. Original maternal records were reviewed and information regarding 10 potential risk factors was extracted. Odds ratios (ORs) were calculated using the Mantel-Haenszel method. Stratification was made for year of delivery, parity (0, I, II, III+), and maternal age (5-year class). Results. In all, 107 infants with shoulder dystocia and 198 controls were included. The OR was greater than unity for all risk factors except gestational age. Three of the risk factors, induction of labor, epidural analgesia, and instrumental delivery, reached statistical significance. Thirty-four infants also suffered brachial plexus injury, giving a brachial plexus injury rate of 32% among the shoulder dystocia cases. We also made a separate analysis of the nine risk factors for brachial plexus injury following a shoulder dystocia, however none reached statistical significance. Conclusion. In this case-control study based on more than 100 000 deliveries at four large hospitals during a 7-year period, induction of labor, epidural analgesia, and instrumental delivery turned out to be significant risk factors for shoulder dystocia. For brachial plexus injury following shoulder dystocia, no significant risk factor was identified.
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8.
  • Darlin, Lotten, et al. (författare)
  • The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm.
  • 2010
  • Ingår i: Gynecologic Oncology. - Academic Press. - 1095-6859. ; 117:2, s. 266-269
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of the study was to evaluate the sentinel node (SLN) concept for lymphatic mapping in early stage cervical cancer. METHODS: 105 women with early stage (1a1-2a) cervical cancer were scheduled for the sentinel node procedure in conjunction with a complete pelvic lymphadenectomy. The day before surgery, 1-1.5 mL 120MBq Tc(99) albumin nanocolloid was injected submucosally at four points around the tumor followed by a lymphoscintigram (LSG) to achieve an overview of the radiotracer uptake. RESULTS: During surgery, the overall detection rate (gamma probe) of at least one SLN was 90% (94/105 women) whereas at least one SLN was identified in 94% (61/65 women) with a tumor </=2 cm. Bilateral SLNs were identified in 62/105 (59%) of the women. Among 18 women with any metastatic lymph node 17 had a metastatic SLN (sensitivity 94%, 95% CI 73-100%). Among 61 women with a tumor </=2 cm, all five women with any metastatic lymph node also had a metastatic SLN (sensitivity 100%). One woman with a 1.5-cm squamous epithelial carcinoma had metastatic positive SLNs on each side but also one metastatic bulky (>2 cm) node without radiotracer uptake. The negative predictive value for patients with cervical cancers </=2 cm was 100%. CONCLUSIONS: The SLN-technique seems to be an accurate method for identifying lymph node metastases in cervical cancer patients with tumors of 2 cm or smaller. In case of a unilateral SLN only, a complete lymphadenectomy should be performed on the radionegative side. All bulky nodes must be removed.
9.
  • Darlin, Lotten, et al. (författare)
  • Vaginal self-sampling without preservative for human papillomavirus testing shows good sensitivity.
  • 2013
  • Ingår i: Journal of Clinical Virology. - Elsevier. - 1386-6532. ; 56:1, s. 52-56
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several strategies have been used to reach non-attending women in organized cervical-cancer-screening programs, with varying success. Self-sampling (SS) for HPV is effective for increasing coverage in screening programs, but requires expensive commercial sampling kits. OBJECTIVE: We aimed to evaluate if vaginal SS, without commercial preservatives was adequate for HPV testing. STUDY DESIGN: Women with abnormal cervical smears as determined from the organized screening program were invited to a colposcopy clinic. The 121 women were asked to insert a cotton swab into the vagina and rotate it, put the cotton swab into a sterile cryotube, break the upper part of the stick and put the cap on. Thereafter, the gynaecologist collected a liquid based cytology (LBC) sample. The presence of HPV-types in SS and LBC samples was analysed with PCR and luminex-based typing. RESULTS: High-risk-HPV (hr-HPV) DNA was found in 65 of the tested 108 SS (60%; 95% CI 0.50-0.69), whereas LBC found hr-HPV in 64/108 samples (59%; 95% CI 0.49-0.69). The agreement between sampling with SS and LBC was good, kappa value 0.67 (95% CI; 0.53-0.81). The sensitivity for SS with hr-HPV to find HSIL was 81% (95% CI; 67-95%), specificity 49% (95% CI; 37-60%) and the sensitivity for LBC with hr-HPV to find HSIL was 90% (95% CI 80-100%), specificity53% (95% CI; 42-65%). CONCLUSIONS: This new vaginal self-sampling method detects hr-HPV-infections with similar sensitivity as a cervical smear taken by a gynaecologist. This self-sampling method is cost-effective and well tolerated, and the kit is suitable for regular mail transport.
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10.
  • Epstein, Elisabeth, et al. (författare)
  • Early-stage cervical cancer: Tumor delineation by magnetic resonance imaging and ultrasound - A European multicenter trial
  • 2013
  • Ingår i: Gynecologic Oncology. - Academic Press. - 1095-6859. ; 128:3, s. 449-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard. Patients and methods. Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2-IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion <2/3 (superficial) or >= 2/3 (deep), and parametrial invasion. Results. Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4 cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2 cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2 cm, or >4 cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was Moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p<0.001) and parametrial invasion (p<0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy. Conclusion. US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion. (C) 2012 Elsevier Inc. All rights reserved.
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