| 1. |
- Andersson, Elin, 1975, et al.
(författare)
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Type-dependent E6/E7 mRNA expression of single and multiple high-risk human papillomavirus infections in cervical neoplasia.
- 2012
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Ingår i: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1873-5967. ; 54:1, s. 61-5
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Tidskriftsartikel (refereegranskat)abstract
- Coinfection with multiple HPV types is common in cervical lesions, but the biological significance of the individual infections is difficult to establish. Expression of oncogenic E6/E7 HPV mRNA is correlated to risk of malignant progression, commercial assays for genotyping E6/E7 mRNA of all HR-HPV are lacking.
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| 2. |
- Andersson, Elin, 1975, et al.
(författare)
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Type-specific HPV E6/E7 mRNA detection by real-time PCR improves identification of cervical neoplasia.
- 2011
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; 49:11, s. 3794-3799
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Tidskriftsartikel (refereegranskat)abstract
- DNA-based HPV assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of oncogenic E6/E7 show higher specificity, but lack either detection of all high-risk HPV genotypes or the capacity to specify the detected genotypes. Therefore, a real-time PCR assay detecting type-specific E6/E7 mRNA was developed and the clinical performance evaluated. 210 cervical LBC (liquid based cytology) samples from 204 women were analysed for HPV DNA and mRNA with the in house real-time PCR as well as PreTect HPV-Proofer. The sensitivity of real-time PCR mRNA-detection to detect histologically confirmed CIN2+ (cervical intraepithelial neoplasia grade 2 or higher) were 0.91, compared to 0.95 for DNA-analysis. The specificity was 0.68 compared to 0.38, and the positive predictive value (PPV) was higher for mRNA (0.67 vs 0.52) without any loss in negative predictive value (NPV). The sensitivity of the real-time PCR mRNA-test was somewhat higher than for PreTect HPV-Proofer (0.83 vs 0.75), when analysing for the same genotypes. The specificity was similar (0.76 vs 0.77). When analysing for mRNA of the eight most common genotypes in cervical cancer (HPV16, 18, 31, 33, 35, 45, 52, 58), the sensitivity to detect CIN2+ lesions was 0.87 and the specificity 0.74, with a PPV of 0.70. In conclusion, real-time PCR for detection of HPV E6/E7 mRNA transcripts can be a sensitive and specific tool in screening and investigation of cervical neoplasia. The composition of HPV-types in mRNA-testing needs to be further investigated to optimize sensitivity and specificity.
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| 3. |
- Beets-Tan, Regina G. H., et al.
(författare)
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Magnetic resonance imaging for the clinical management of rectal cancer patients : recommendations from the 2012 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting
- 2013
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 23:9, s. 2522-2531
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Tidskriftsartikel (refereegranskat)abstract
- To develop guidelines describing a standardised approach regarding the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. A consensus meeting of 14 abdominal imaging experts from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) was conducted following the RAND-UCLA Appropriateness Method. Two independent (non-voting) chairs facilitated the meeting. Two hundred and thirty-six items were scored by participants for appropriateness and classified subsequently as appropriate or inappropriate (defined by a parts per thousand yen 80 % consensus) or uncertain (defined by < 80 % consensus). Items not reaching 80 % consensus were noted. Consensus was reached for 88 % of items: recommendations regarding hardware, patient preparation, imaging sequences, angulation, criteria for MRI assessment and MRI reporting were constructed from these. These expert consensus recommendations can be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI. These guidelines recommend standardised imaging for staging and restaging of rectal cancer. The guidelines were constructed through consensus amongst 14 abdominal imaging experts. Consensus was reached by in 88 % of 236 items discussed.
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| 4. |
- Farnebo, Jacob, et al.
(författare)
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Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 14, s. 408-
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Tidskriftsartikel (refereegranskat)abstract
- Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression-free patient survival. Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression-free survival. Results: Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression-free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Conclusions: Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression-free and overall survival in patients with mRCC.
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| 5. |
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| 6. |
- Hedlund, Anna, 1973-
(författare)
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MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.
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| 7. |
- Mosavi, Firas
(författare)
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Whole-Body MRI including Diffusion-Weighted Imaging in Oncology
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is one of the major causes of worldwide mortality. Imaging plays a vital role in the staging, follow-up, and evaluation of therapeutic response in cancer patients. Whole-body (WB) magnetic resonance imaging (MRI), as a non-ionizing imaging technique, is a promising procedure to assess tumor spreading in a single examination. New MRI technological developments now enable the application of diffusion-weighted imaging (DWI) of the entire body. DWI reflects the random motion of water molecules and provides functional information of body tissues. DWI can be quantified with the use of the apparent diffusion coefficient (ADC). The aim of this dissertation was to demonstrate the value of WB MRI including DWI in cancer patients.WB MRI including DWI, 18F-NaF PET/CT, and bone scintigraphy was performed on 49 patients with newly diagnosed, high-risk prostate cancer, for the purpose of detecting bone metastases. WB DWI showed higher specificity, but lower sensitivity compared to 18F-NaF PET/CT. In addition, WB MRI including DWI, and CT of the chest and abdomen was performed in 23 patients with malignant melanoma. We concluded that WB MRI could not completely supplant CT for the staging of malignant melanoma, especially with respect to the detection of lesions in the chest region. In this study, WB MRI and DWI were able to detect more bone lesions compared to CT, and showed several lesions outside the CT field of view, reinforcing the advantage of whole-body examination.WB MRI, including DWI, was performed in 71 patients with testicular cancer. This modality demonstrated its feasibility for use in the follow-up of such patients. WB MRI, including DWI, and 18F-FDG PET-CT, were carried out in 50 patients with malignant lymphoma. Both these imaging modalities proved to be promising approaches for predicting clinical outcomes and discriminating between different subtypes of lymphomas.In conclusion, WB MRI, including DWI, is an evolving technique that is continuing to undergo technical refinement. Standardization of image acquisition and analysis will be invaluable, allowing for more accurate comparison between studies, and widespread application of this technique in clinical practice. Both WB MRI, including DWI and PET/CT, have their particular strengths and weaknesses in the evaluation of metastatic disease. DWI and PET/CT are different functional techniques, so that combinations of these techniques may provide complementary and more comprehensive information of tumor tissue.
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| 8. |
- Nilsson, Per J., et al.
(författare)
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Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer - the RAPIDO trial
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 13, s. 279-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Methods and design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.
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| 9. |
- Rollven, Erik, et al.
(författare)
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Potentials of high resolution magnetic resonance imaging versus computed tomography for preoperative local staging of colon cancer
- 2013
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 54:7, s. 722-730
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preoperative identification of locally advanced colon cancer is of importance in order toproperly plan treatment. Purpose: To study high resolution T2-weighted magnetic resonance imaging (MRI) versus computed tomography (CT) for preoperative staging of colon cancer with surgery and histopathology as reference standard. Material and Methods: Twenty-eight patients with a total of 29 tumors were included. Patients were examined on a 1.5 T MR unit using a phased array body coil. T2 turbo spin-echo high resolution sequences were obtained in a coronal, transverse, and perpendicular plane to the long axis of the colon at the site of the tumor. Contrast-enhanced CT was performed using a protocol for metastasis staging. The examinations were independently evaluated by two gastrointestinal radiologists using criteria adapted to imaging for prediction of T-stage, N-stage, and extramural venous invasion. Based on the T-stage, tumors were divided in to locally advanced (T3cd-T4) and not locally advanced (T1-T3ab). Surgical and histopathological findings served as reference standard. Results: Using MRI, T-stage, N-stage, and extramural venous invasion were correctly predicted for each observer in 90% and 93%, 72% and 69%, and 82% and 78% of cases, respectively. With CT the corresponding results were 79% and 76%, 72% and 72%, 78% and 67%. For MRI inter-observer agreements (Kappa statistics) were 0.79, 0.10, and 0.76. For CT the corresponding results were 0.64, 0.66, and 0.22. Conclusion: Patients with locally advanced colon cancer, defined as tumor stage T3cd-T4, can be identified by both high resolution MRI and CT, even when CT is performed with a metastasis staging protocol. MRI may have an advantage, due to its high soft tissue discrimination, to identify certain prognostic factors such as T-stage and extramural venous invasion.
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| 10. |
- Suzuki, Chikako, et al.
(författare)
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Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy
- 2013
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Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this was to determine whether the change of size observed at the first response evaluation after initiation of first-line combination chemotherapy correlates with overall survival (OS) in patients with metastatic breast cancer (MBC). The change in size of tumors derived from measurements according to Response Evaluation Criteria In Solid Tumors (RECIST) at the first evaluation on computed tomography (CT) was obtained from a multicenter, randomized phase III trial ("TEX trial," n = 287) comparing treatment with a combination of epirubicin and paclitaxel alone or with capecitabine (TEX). Cox regression and Kaplan-Meier analyses were performed to evaluate the correlations between the first change in tumor size, response according to RECIST and OS. Data from CT evaluations of 233 patients were available. Appearance of new lesions or progression of non-target lesions (new/non-target) indicated short OS by univariable regression analysis (HR 3.76, 95 % CI 1.90-7.42, p andlt; 0.001). A decrease by andgt;30 % at this early time point was prognostic favorable (HR 0.69, 95 % CI 0.49-0.98, p = 0.04) and not significantly less than the best overall response according to RECIST. After adjustment for previous adjuvant treatment and the treatment given within the frame of the randomized trial, OS was still significantly shorter in patients with new/non-target lesions after a median 8 weeks of treatment (HR 4.41, 95 % CI 2.74-7.11, p andlt; 0.001). Disease progression at the first evaluation correlates with OS in patients with MBC treated with first-line combination chemotherapy. The main reason for early disease progression was the appearance of new lesions or progression of non-target lesions. These patients had poor OS even though more lines of treatment were available. Thus, these factors should be focused on in the response evaluations besides tumor size changes.
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