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- Andreasson, Kalle
(författare)
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Vaccination against Her2/neu : expressing cancer using chimeric virus-like particles
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thanks to the development of vaccines, children are these days protected against infectious diseases like polio, diphtheria and tetanus simply by receiving a few injections. Imagine a scenario where these injections would also result in protection against cancer. Vaccines against virus-induced cancer such as liver and cervical cancer are indeed already in use. Intense research is now focused on the generation of vaccines for protection also against cancer not induced by viruses. The overall aim of this thesis was to develop and determine the pre-clinical efficacy of a vaccine against tumours expressing the antigen Her2/neu. Polyomaviruses are small non-enveloped viruses that are widespread in the population, and probably harmless as long as the immune system is normal. The viral capsid is composed of three structural proteins, the major structural protein VP1, and the two minor proteins VP2 and VP3. The mouse is host to two known polyomaviruses, murine polyomavirus (MPyV) and murine pneumotropic virus (MPtV), respectively. It was known from before that VP1 of MPyV could self-assemble into viral capsids known as virus-like particles (VLPs), named so because of their morphological resemblance to natural viruses. In paper I, we showed that VP1 of MPtV could also self-assemble into VLPs, which were rapidly internalized by all tested cell types, including dendritic cells. However, the VLPs were not very efficient as vectors for gene therapy, possibly due to poor delivery of DNA into the nucleus of target cells. The combination of efficient cellular uptake and poor nuclear delivery indicated that the VLPs could be more efficient as carriers of proteins for presentation to the immune system, since delivery into the cytoplasm would be sufficient in that case. We therefore attached Her2/neu to the inside of VLPs of both MPyV and MPtV and obtained so-called chimeric VLPs (cVLPs). In papers II and III, we showed that Her2/neu-cVLPs could protect against outgrowth of transplantable Her2/neu-expressing tumours in normal mice, as well as against spontaneously arising Her2/neu-positive carcinomas in transgenic mice. Her2/neu-cVLPs from MPtV also induced immunological memory and protected against tumour out-growth in a therapeutic setting. The purpose of paper IV was to determine the immune mechanisms responsible for tumour protection. We could demonstrate that Her2/neu-cVLPs induced Her2/neu-specific CD8+ T cells, but did not induce anti-Her2/neu antibodies. However, we observed that mice were protected against tumour development also after depletion of either CD8+, or CD4+ T cells, but not after combined depletion of CD4+ and CD8+ T cells. This indicated that CD4+ T cells could compensate for the absence of CD8+ T cells and mediate tumour protection by a yet not fully clarified mechanism independent of both antibodies and CD8+ T cells. In conclusion, in this thesis it is shown that Her2/neu-cVLPs based on both MPyV and MPtV are efficient as prophylactic and therapeutic vaccines against Her2/neu-expressing tumours in mice, and that protection involves both CD4+ and CD8+ T cells.
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| 2. |
- Chabok, Abbas, 1964-, et al.
(författare)
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Low risk of complications in patients with first-time acute uncomplicated diverticulitis
- 2017
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Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 32:12, s. 1699-1702
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Tidskriftsartikel (refereegranskat)abstract
- First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Vastmanland's Hospital, VasterAs, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD.
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| 3. |
- Enlund, Mats, et al.
(författare)
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The choice of anaesthetic - sevoflurane or propofol - and outcome from cancer surgery : a retrospective analysis
- 2014
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 119:3, s. 251-261
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia.PATIENTS AND METHODS:Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders.RESULTS:Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant.CONCLUSION:Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.
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| 4. |
- Isacson, Daniel, et al.
(författare)
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No antibiotics in acute uncomplicated diverticulitis : does it work?
- 2014
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 49:12, s. 1441-1446
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Tidskriftsartikel (refereegranskat)abstract
- Background. The first randomized multicenter study evaluating the need for antibiotic treatment in patients with acute uncomplicated diverticulitis (AUD) could not demonstrate any benefit gained from antibiotic use. The aim of this study was to review the application of the no antibiotic policy and its consequences in regard to complications and recurrence. Methods. This retrospective population-based cohort study included all patients diagnosed with all types of colonic diverticulitis during the year 2011 at Vastmanland Hospital Vasteras, Sweden. All medical records were carefully reviewed. Primary outcomes were the types of treatment adopted for diverticulitis, complications and recurrence. Results. In total, 246 patients with computer tomography-verified diverticulitis were identified, 195 with primary AUD and 51 with acute complicated diverticulitis. Age, sex, and temperature at admission were similar between the groups but there was a significant difference in white blood cell count, C-reactive protein, and length of hospital stay. In the AUD group, 178 (91.3%) patients were not treated with antibiotics. In this group, there were six (3.4%) readmissions but only two developed an abscess. Of the remaining 17 patients (8.7%) who were treated with antibiotics in the AUD group, one developed an abscess. Twenty-five (12.8%) patients in the AUD group presented with a recurrence within 1 year. Conclusion. The no-antibiotic policy for AUD is safe and applicable in clinical practice. The previous results of a low complication and recurrence rate in AUD are confirmed. There is no need for antibiotic treatment for AUD. What does this paper add to the literature? Despite published papers with excellent results, there are still doubts about patient safety against the policy to not use antibiotics in acute uncomplicated diverticulitis. This is the first paper, in actual clinical practice, to confirm that the no antibiotic policy for acute uncomplicated diverticulitis is applicable and safe.
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| 5. |
- Piccoli, Francesco, et al.
(författare)
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FuSSI-Net: Fusion of Spatio-temporal Skeletons for Intention Prediction Network
- 2020
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Ingår i: Conference Record - Asilomar Conference on Signals, Systems and Computers. - 1058-6393. ; 2020-November, s. 68-72
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Konferensbidrag (refereegranskat)abstract
- Pedestrian intention recognition is very important to develop robust and safe autonomous driving (AD) and advanced driver assistance systems (ADAS) functionalities for urban driving. In this work, we develop an end-to-end pedestrian intention framework that performs well on day- and night- time scenarios. Our framework relies on objection detection bounding boxes combined with skeletal features of human pose. We study early, late, and combined (early and late) fusion mechanisms to exploit the skeletal features and reduce false positives as well to improve the intention prediction performance. The early fusion mechanism results in AP of 0.89 and precision/recall of 0.79/0.89 for pedestrian intention classification. Furthermore, we propose three new metrics to properly evaluate the pedestrian intention systems. Under these new evaluation metrics for the intention prediction, the proposed end-to-end network offers accurate pedestrian intention up to half a second ahead of the actual risky maneuver.
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