| 31. |
- Tassidis, Helena, et al.
(författare)
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Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
- 2010
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 126:10, s. 2296-2307
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Tidskriftsartikel (refereegranskat)abstract
- The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here, we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient and stable transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation, whereas in SHP-1-silenced LNCaP cells, IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer.
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| 32. |
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| 33. |
- Paulsson, Kajsa, et al.
(författare)
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Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia
- 2010
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Ingår i: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - : National Academy of Sciences; 1999. - 0027-8424 .- 1091-6490. ; 107:50, s. 21719-21724
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Tidskriftsartikel (refereegranskat)abstract
- High hyperdiploid acute lymphoblastic leukemia ( ALL) is one of the most common malignancies in children. It is characterized by gain of chromosomes, typically +X, +4, +6, +10, +14, +17, +18, and +21, +21; little is known about additional genetic aberrations. Approximately 20% of the patients relapse; therefore it is clinically important to identify risk-stratifying markers. We used SNP array analysis to investigate a consecutive series of 74 cases of high hyperdiploid ALL. We show that the characteristic chromosomal gains are even more frequent than previously believed, indicating that karyotyping mistakes are common, and that almost 80% of the cases display additional abnormalities detectable by SNP array analysis. Subclonality analysis strongly implied that the numerical aberrations were primary and arose before structural events, suggesting that step-wise evolution of the leukemic clone is common. An association between duplication of 1q and +5 was seen ( P = 0.003). Other frequent abnormalities included whole-chromosome uniparental isodisomies ( wUPIDs) 9 and 11, gain of 17q not associated with isochromosome formation, extra gain of part of 21q, deletions of ETS variant 6 (ETV6), cyclin-dependent kinase inhibitor 2A (CKDN2A) and paired box 5 (PAX5), and PAN3 poly(A) specific ribonuclease subunit homolog (PAN3) microdeletions. Comparison of whole-chromosome and partial UPID9 suggested different pathogenetic outcomes, with the former not involving CDKN2A. Finally, two cases had partial deletions of AT rich interactive domain 5B (ARID5B), indicating that acquired as well as constitutional variants in this locus may be associated with pediatric ALL. Here we provide a comprehensive characterization of the genetic landscape of high hyperdiploid childhood ALL, including the heterogeneous pattern of secondary genetic events.
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| 34. |
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| 35. |
- Bratt, Ola, et al.
(författare)
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Prostate cancer diagnosed after prostate-specific antigen testing of men without clinical signs of the disease : a population-based study from the National Prostate Cancer Register of Sweden
- 2010
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 44:6, s. 384-390
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the effects of prostate-specific antigen (PSA) testing of men without clinical signs of prostate cancer on the incidence of prostate cancer in Sweden. Material and methods. Information on the cause of diagnosis, tumour characteristics and primary treatment for patients diagnosed with prostate cancer between January 1999 and December 2007 was extracted from the National Prostate Cancer Register of Sweden. This register includes data for 95% of Swedish prostate cancer cases. Results. The total age-standardized annual incidence of prostate cancer per 100 000 men increased from 187 in 1999 to 233 in 2004, but decreased thereafter to 196 in 2007. The incidence of asymptomatic cases also peaked in 2004 (at 62 per 100 000 men), but varied six-fold between different counties in that year (16–98 per 100 000 men). Asymptomatic cases (n = 17 143) constituted 15% of all new cases in 2000 and 30% in 2007. Almost as many cases were diagnosed in stage T1c in men with symptoms, usually from the lower urinary tract. Together these two groups constituted 29% of all new cases in 2000 and 52% in 2007. It was estimated that at least one-third of all Swedish men aged 50–75 years had a PSA test between 2000 and 2007. Conclusions. Even though screening for prostate cancer is not recommended in Sweden, PSA testing of men without clinical signs of prostate cancer is common. The effects on the Swedish incidence of prostate cancer were similar to those reported from the USA.
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| 36. |
- Jonsson, Annikki, 1949, et al.
(författare)
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Living with a prostate cancer diagnosis: a qualitative 2-year follow-up.
- 2010
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Ingår i: AGING MALE. - : Informa UK Limited. - 1368-5538 .- 1473-0790. ; 13:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Aim. Previous research has identified how newly diagnosed prostate cancer affects men's daily lives, including daily activities and existential issues. The aim of this qualitative study was to provide information if and how prostate cancer affects men's daily lives 2 years after the diagnosis. Methods. A second follow-up interview with men who were diagnosed with localized or advanced prostate cancer approximately 18-24 months earlier. Twenty-two men aged 50-85 years participated, data were analyzed by hermeneutical interpretation with Gadamer's approach. Results. The men feel healthy, but prostate cancer affects their daily lives. They experience every day fatigue associated with several changes in life due to age. Three equivalent fusions which influenced the men are: 'Age is claiming its due', 'Living with uncertainty', and 'Strengthen self-esteem'. The unifying fusion is identified as 'Balancing a changed life situation.' Conclusions. There is need for knowledge and guidance for men with prostate cancer on how to adapt to new life situation decreasing uncertainty and increasing welfare. Men found a sense of pride, despite physical changes, in appreciating independence and close relationships. Value of life was readjusted. The findings indicate harmony in living, enjoying being frank as well as rating the 'little' things.
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| 37. |
- Gunnlaugsson, Adalsteinn
(författare)
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Chemoradiation in Gastrointestinal Cancer
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Locally advanced inextirpable gastrointestinal cancer has poor prognosis and is associated with high morbidity. One treatment option is to use radiotherapy, often combined with chemotherapy (chemoradiation), either as preoperative treatment to facilitate surgery or in the palliative setting to relieve symptoms. The aim of this thesis was to investigate efficacy and toxicity of intensive chemoradiation including conformal radiotherapy and newer chemotherapeutic agents. Oxaliplatin and capecitabine together with 50 Gy radiotherapy was used in a national phase I-II study (CORGI), divided in two parts by tumor location. Among 61 patients with locally advanced colorectal cancer, primary tumor or local recurrence, with or without distant metastases, the objective local response rate was 58% and 79% went to surgical resection (paper I) The main side-effect was diarrhea. 39 patients with pancreatic or biliary tract cancer were included (paper II). The maximum tolerated chemotherapy doses were determined. Dose-limiting toxicity was nausea/vomiting. The local response rate was 21 %. In both CORGI studies there was a high frequency of sustained local control at two years. The most important risk factor for diarrhea during chemoradiation was the volume of small bowel that received >15 Gy (paper III). Enteritis is thought to be mediated by eradication of intestinal crypts. In a mouse model we found that adding oxaliplatin and 5-FU to radiation increased the mucosal damage (paper IV). Thus, chemoradiation is effective and feasible in several types of gastrointestinal cancers. Sparing small bowel from radiation is important.
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| 38. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Sublingual administration of fentanyl to cancer patients is an effective treatment for breakthrough pain: results from a randomized phase II study.
- 2010
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Ingår i: Palliative medicine. - : SAGE Publications. - 1477-030X .- 0269-2163. ; 24:3, s. 286-93
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Tidskriftsartikel (refereegranskat)abstract
- In this study we evaluated the efficacy and tolerability of sublingual fentanyl (SLF) for breakthrough pain (BTP) in adult opioid-tolerant cancer patients. Patients received one dose of placebo, SLF 100, 200 and 400 microg in random order at four pain episodes. The primary efficacy endpoint was pain intensity difference (PID) from baseline. Twenty-seven patients received study medication. Overall PID increased significantly with SLF 400 microg versus placebo (8.57 mm, p <0.0001). Improvements were statistically different from placebo at 15 min (p = 0.005). SLF 100 and 200 microg showed a numerical trend towards improved pain relief. A dose that gave a clinically important reduction in pain (PID > 20 mm) was identified by 95% of patients. Reduced use of rescue medication (p < 0.001, SLF 400 microg) and improved global assessment of treatment (p = 0.0146, SLF 400 microg) confirmed these differences as clinically important. Nausea and dizziness were the most common treatment-related adverse effects. SLF appears to be a fast, effective and well-tolerated treatment for BTP.
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| 39. |
- Fallbjörk, Ulrika, 1967-, et al.
(författare)
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Differences between women who have and have not undergone breast reconstruction after mastectomy due to breast cancer
- 2010
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 49:2, s. 174-179
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study compares potential differences between women with breast cancer who after mastectomy had undergone breast reconstruction with those who had not. Material and methods: All women (N=149) in the northern medical region of Sweden who had undergone mastectomy in 2003 received a self-reported questionnaire entitled “Life After Mastectomy (LAM)” that included standardized measures of sociodemographic, decision-making process, breast reconstruction (BR) yes or no, sexuality, and body image. SPSS was used for data processing. Results: In total 85% of the women returned the questionnaire and of these 25% had undergone BR. In accordance with previous studies, we found that the mean age of the women in the BR group was significantly lower (52 vs. 64 years), they had a higher education, and a higher proportion were employed, influenced by the physician's opinion regarding BR, sexually active, and rated a negative impact concerning the factors attractiveness and body disclosure. A multiple regression analysis, however, showed that the choice to undergo breast reconstruction or not was only independently associated with age, feeling of attractiveness and sexual interest. Discussion: Age explained most differences found between the two groups. When researchers try to identify what differentiates the groups of women who undergo reconstruction between those who do not undergo reconstruction after mastectomy, it is thus necessary to take into consideration that the meanings of mastectomy, body image, attractiveness and similar variables may vary due to the phase of a woman's life. In conclusion, considering the impact of age is of paramount importance in future studies for our understanding of women's experiences.
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| 40. |
- Silverplats, Katarina, 1969, et al.
(författare)
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Clinical factors of importance for outcome after lumbar disc herniation surgery : long-term follow-up
- 2010
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Ingår i: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 19:9, s. 1459-1467
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Tidskriftsartikel (refereegranskat)abstract
- Factors as age, sex, smoking, duration of leg pain, working status, type/level of disc herniation and psychosocial factors have been demonstrated to be of importance for short-term results after lumbar discectomy. There are few studies with long-term follow-up. In this prospective study of lumbar disc herniation patients undergoing surgery, the result was evaluated at 2 and 5-10 (mean 7.3) years after surgery. Predictive factors for satisfaction with treatment and objective outcome were investigated. Out of the included 171 patients undergoing lumbar discectomy, 154 (90%) patients completed the 2-year follow-up and 140 (81%) completed the long-term follow-up. Baseline data and questionnaires about leg- and back pain intensity (VAS), duration of leg pain, disability (Oswestry Disability Index), depression (Zung Depression Scale), sick leave and employment status were obtained preoperatively, at 2-year- and long-term follow-up. Primary outcome included patient satisfaction with treatment (at both time points) and assessment of an independent observer at the 2-year follow-up. Secondary outcomes at 2-year follow-up were improvement of leg and back pain, working capacity and the need for analgesics or sleeping pills. In about 70% of the patients excellent or good overall result was reported at both follow-ups, with subjective outcome measurements. The objective evaluation after 2 years was in agreement with this result. Time on sick leave was found to be a clinically important predictor of the primary outcomes, with a potential of changing the probability of a satisfactory outcome (both objective and subjective) from around 50% (sick leave >3 months) to 80% (sick leave <2 months). Time on sick leave was also an important predictor for several of the secondary outcomes; e.g. working capacity and the need for analgesics.
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