| 1. |
- Ellin, Fredrik, et al.
(författare)
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Central nervous system relapse in peripheral T-cell lymphomas: A Swedish lymphoma registry study.
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:1, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Central Nervous System (CNS) relapse in non-Hodgkin lymphomas (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, and the outcome of these patients, in a large population-based cohort of PTCL patients. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis disease characteristics at diagnosis independently associated with an increased risk of later CNS involvement were involvement of >1 extranodal site (Hazard Ratio [HR] 2.60, 95% Confidence Interval [95% CI] 1.07-6.29, p=0.035), skin (HR 3.51, 95% CI 1.26-9.74, p=0.016) and gastrointestinal involvement (HR 3.06, 95% CI 1.30-7.18, p=0.010). The outcome of relapsed/refractory patients was very poor and CNS involvement was not associated with a significantly worse outcome compared to relapsed/refractory patients without CNS involvement in multivariable analysis (HR 1.6, 95% CI 0.96-2.6, p=0.074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.
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| 2. |
- Ellin, Fredrik, et al.
(författare)
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Real world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry.
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:10, s. 1570-1577
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral T-cell Lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. Addition of etoposide to CHOP and up-front consolidation with autologous stem cell transplantation (autoSCT) have shown promising results, but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index (IPI) factors, male gender was associated with an adverse overall survival (OS) (HR 1.28, p=0.011) and progression-free survival (PFS) (HR 1.26, p=0.014). In an intention-to-treat analysis in 252 nodal PTCL and EATL patients (excluding ALK-positive ALCL), up-front autoSCT was associated with a superior OS (HR 0.58, p=0.004) and PFS (HR 0.56, p=0.002) compared to patients treated without autoSCT. Addition of etoposide to CHOP resulted in superior PFS in patients up to 60 years (HR 0.49, p=0.008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials.
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| 3. |
- Schell-Leugers, Jenny, et al.
(författare)
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Police Suspect Interviewing: A Self-Report Survey of Police Practices and Beliefs in Europe
- 2019
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Ingår i: The 12th Annual Conference of the International Investigative Interviewing Research Group (iIIRG), Stavern, Norway.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- On a daily basis, thousands of suspects all around the world are interviewed. While police detectives are trying to find out whether a suspect has been involved in a crime, suspects often feel intimidated during an interrogation, especially those who are innocent. In recent years, the detection of wrongful convictions in America, often with DNA evidence, has highlighted the impact of coercive interrogation techniques on innocent suspects. However, police interrogations are vital to the process of solving crimes and serving justice. To get a better picture in how far common police practices can play a role in wrongful convictions, Kassin and colleagues (2007) surveyed 631 North American police investigators to examine their interrogation beliefs and practices. They constructed a questionnaire in which the participants, were asked to report on six topics: deception detection, Miranda warnings, interrogation techniques, interviews and interrogations, confession rates, and the recording of interrogations. The findings from this survey gave insight into what happens in North American interrogation rooms. To the best of our knowledge, no previous study has examined the beliefs and practices of European police investigators. It is important to note that many European countries operate under an inquisitorial legal system and that suspect interviews have shifted from a more accusatorial towards an information gathering approach in recent years. Furthermore, the Salduz ruling resulted in reformed procedures concerning legal assistance during interrogations, which may had an impact on interrogation practices as well. However, little is known about what actually happens in interrogations in Europe. In an effort to better understand how experienced investigators in different European countries approach the processes of interviewing and interrogation, we are seeking to replicate the self-report survey of North American police practices and beliefs by Kassin and colleagues (2007). We are employing an adapted version of their instrument, covering investigators’ beliefs and practices about 1) their ability to detect truth and deception, 2) suspects’ willingness to talk to the police, 3) the use of various interrogation techniques, 4) the frequency and length of interviews and interrogations, 5) the rates of true and false confessions, and 6) their own practices and opinions with regard to the recording of interrogations and confessions. Our goal is to explore and compare police practices and beliefs in six European countries (Belgium, Germany, Netherlands, Norway, Spain and Sweden), and to compare – where possible - the data collected in this sample to those previously obtained in North America. The potential benefits of the study are important for questions pertaining to investigators’ self-reported interrogation practices, beliefs and perceptions. We believe that the potential benefit of the proposed research is substantial. It will aid to gain knowledge about common practices used by investigators and the results might help with reforming certain police practices.
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| 4. |
- Wang, Tianyan, 1983-
(författare)
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Utility of novel drug targets for treatment of metastatic cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metastasis is the leading cause of cancer death because of a lack of early diagnosis tools and efficient treatment drugs. The lipid kinase phosphatidylinositol 4-phosphate 5 kinase (PIP5K1α) has been shown to play a vital role in the PI3K/AKT and KRAS signaling pathways. My PhD work, therefore, aims: (i) to study the role of PIP5K1α as a potential target for cancer treatment and the utility of its inhibitor ISA-2011B for the treatment of castration-resistant prostate cancer (CRPC) and pancreatic cancer, (ii) to establish genetically engineered mouse models and murine syngeneic models to recapitulate pancreatic cancer progression and test targeted anticancer drugs, (iii) to utilize the state-of-the-art molecularly imprinting technique for cancer biomarker detection.My thesis work has shown a clear inhibitory effect of ISA-2011B on human CRPC cell lines C4-2, DU145, and PC-3. The siRNA-mediated downregulation of PIP5K1α and ISA-2011B treatments both showed inhibition of the in vitro growth in all three cell lines. The PC-3 cell and its xenograft tumor can be inhibited by tamoxifen or ISA-2011B treatment alone, and a combination treatment from both compounds can selectively block the ERα and PIP5K1α/AKT network. The results, therefore, suggest that it is possible to treat CRPC by targeting PIP5K1α/AKT and ERα pathways.We established the KPC [Krastm4Tyj Trp53tm1Brn Tg(Pdx1-Cre/Esr1*)] mouse model, in which spontaneous pancreatic ductal adenocarcinoma (PDAC) develops under tamoxifen induction. Three PDAC cell lines bearing KRASG12D and P53 mutations from spontaneous tumors were established and characterized. ISA-2011B in vitro treatment on those cell lines showed that KRASG12D and pErk were significantly decreased in at least one of the cell lines. It suggests that PIP5K1α is a potential target, and its inhibitor ISA-2011B is a promising drug for treating KRAS-mutated PDAC. The syngeneic PDAC model was also prepared by subcutaneous injection of the three cell lines back into the KPC mice, which will be used as an in vivo model to study the function of PIP5K1α in PDAC further.We developed molecularly imprinted polymers (MIPs) for the potential biomarker Neu5Acα2-6GalNAcα-O-Ser/Thr (STn), as well as the non-imprinted polymers(NIPs) as a control. We identified human PDAC cell lines CFPAC-1 and BxPC-3 are STn-positive and -negative cells, respectively. Although STn-MIPs have a higher affinity than NIPs to both cancer cell lines, STn-MIPs cannot differentiate the STn-positive CFPAC-1 cells from the STn-negative BxPC-3 cells. It remains challenging to apply MIPs to detect biological molecules.Our data provide a novel therapeutic strategy to treat advanced cancers such as CRPC and KRAS-mutated PDAC by targeting PIP5K1α-associate PI3K/AKT and/or KRAS signaling pathways.
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