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- Lindegren, Sture, 1960, et al.
(author)
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Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.
- 2015
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Journal article (peer-reviewed)abstract
- The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.
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| 2. |
- Barywani, Salim B., 1968, et al.
(author)
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Predictors of long-term outcome of percutaneous coronary intervention in octogenarians with acute coronary syndrome
- 2014
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In: IJC Heart and Vessels. - : Elsevier BV. - 2214-7632. ; 4:1, s. 138-144
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Journal article (peer-reviewed)abstract
- The majority of patients with acute coronary syndrome (ACS) are elderly. Limited evidence makes decision-making on the use of percutaneous coronary intervention (PCI) mainly empirical. Old age is one risk factor, but other factors than age may have an impact on mortality as well. Therefore, we investigated predictors of long-term all-cause mortality among octogenarians who have undergone PCI due to ACS. A total of 182 patients ≥. 80 years who underwent PCI during 2006-2007 at Sahlgrenska University Hospital were studied consecutively from recorded clinical data. All-cause five-year mortality of follow-up was 46.2%. Mean age was 83.7. ±. 2.8, 62% were male, 76% were in sinus rhythm, and 42% had left ventricular ejection fraction. < 45%. Indications for PCI were STEMI (52%), NSTEMI (36%) and unstable angina (11%). Multivariate analysis in two steps identified atrial fibrillation, moderate tricuspid valve regurgitation, moderate mitral valve regurgitation, dependency in ADL and eGFR. ≤. 30. ml/min at the first step and moderate mitral valve regurgitation, atrial fibrillation and eGFR. ≤. 30 ml/min at the last step, as independent predictors of all-cause mortality. Kaplan Meier analysis of positive parameters from both steps of multivariate analysis showed high significant difference in survival between patients having these parameters and those who were free from these parameters, with worst prognosis in patients with accumulation of these parameters. Accordingly, we have, in an octogenarian patient cohort who suffered from ACS, undergone PCI in daily clinical practice, identified five prognostic predictors for all-cause death after five years' follow-up.
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| 5. |
- Hagman, H., et al.
(author)
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A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer : the Nordic ACT2 trial
- 2016
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:1, s. 140-147
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Journal article (peer-reviewed)abstract
- Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.
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| 6. |
- Kotti, Angeliki, et al.
(author)
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SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients
- 2014
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 88:5, s. 1196-1202
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Journal article (peer-reviewed)abstract
- PurposeThe secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.Methods and MaterialsThe study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.ResultsTumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).ConclusionsSPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.
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| 7. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(author)
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Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
- 2001
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In: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 86:7, s. 3039-44
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Journal article (peer-reviewed)abstract
- The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
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| 8. |
- Brosved, Madeleine, et al.
(author)
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Effects of Cardiac Rehabilitation on Physical Fitness, Physical Function, and Self-reported Outcomes in Patients ≥80 yr: A RANDOMIZED CONTROLLED TRIAL.
- 2022
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In: Journal of cardiopulmonary rehabilitation and prevention. - 1932-751X. ; 42:5, s. 331-337
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Journal article (peer-reviewed)abstract
- The beneficial effects of exercise-based cardiac rehabilitation (CR) after an acute coronary syndrome (ACS) are well known, but patients ≥80 yr have been less studied. The aim was to evaluate the effects of CR on patients with ACS ≥80 yr on peak cardiorespiratory fitness (CRF), physical function, and patient-reported outcome measures (PROMs) compared with a control group.A total of 26 patients with ACS, median age 82 (81, 84) yr, were randomized to hospital-based CR combined with a home-based exercise program (CR group) or to a control group (C) for 4 mo. Outcomes were assessed at baseline and 4 mo and included the peak CRF (primary outcome), 6-min walk test (6MWT), muscle endurance, Timed Up and Go (TUG), Short Physical Performance Battery (SPPB), one-leg stand test, and PROMs.There were no significant differences between the groups in peak CRF. The CR group improved significantly in terms of the 6MWT ( P = .04), isotonic muscle endurance ( P < .001), one-leg stand test ( P = .001), SPPB total score ( P =.03), Activities-specific Balance Confidence ( P =.01), and anxiety ( P =.03), as compared with C. There were no significant intergroup differences in the TUG, the self-reported health question or depression.Patients with ACS ≥80 yr improved in walking distance, muscle endurance, physical function, and PROMs, but not in peak CRF, by participating in a CR program. These results suggest an increased referral to CR for this growing group of patients to enable preserved mobility and independence in daily living, but this needs to be confirmed in larger studies.
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| 9. |
- Chaplin, John, 1955, et al.
(author)
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When Do Short Children Realize They Are Short? : Prepubertal Short Children's Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment
- 2012
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In: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 77:4, s. 241-249
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Journal article (peer-reviewed)abstract
- Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children's and parents' responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother's height, parental sense of the child's tallness and age explained more variance in children's sense of tallness (34%) than measured height (0%). Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.
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