| 1. |
- Lindegren, Sture, 1960, et al.
(författare)
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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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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)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. |
- Andersson, Ellen, et al.
(författare)
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GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs
- 2017
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Ingår i: Clinical Practice. - : Future Medicine. - 2044-9038 .- 2044-9046. ; 14:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.
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| 3. |
- Barywani, Salim B., 1968, et al.
(författare)
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Acute coronary syndrome in octogenarians: association between percutaneous coronary intervention and long-term mortality
- 2015
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Ingår i: Clinical Interventions in Aging. - : Informa UK Limited. - 1178-1998. ; 10, s. 1547-1553
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Evidence of improved survival after use of percutaneous coronary intervention (PCI) in elderly patients with acute coronary syndrome (ACS) is limited. We assessed the association between PCI and long-term mortality in octogenarians with ACS. Methods and results: We followed 353 consecutive patients aged >= 80 years hospitalized with ACS during 2006-2007. Among them, 182 were treated with PCI, whereas 171 were not. PCI-treated patients were younger and more often male, and had less stroke and dependency in activities of daily living, but there were no significant differences in occurrence of diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and uncured malignancies between the two groups. The association between PCI and all-cause mortality was assessed in the overall cohort and a 1: 1 matched cohort based on propensity score (PS). In overall cohort, 5-year all-cause mortality was 46.2% and 89.5% in the PCI and non-PCI groups, respectively. Cox regression analysis in overall cohort by adjustment for ten baseline variables showed statistically significant association between PCI and reduced long-term mortality (P < 0.001, hazard ratio 0.4, 95% confidence interval [CI] 0.2-0.5). In propensity-matched cohort, 5-year all-cause mortality was 54.9% and 83.1% in the PCI and non-PCI groups, respectively. Kaplan-Meier survival curves and log rank test showed significantly improved mean survival rates (P=0.001): 48 months (95% CI 41-54) for PCI-treated patients versus 35 months (95% CI 29-42) for non-PCI-treated patients. Furthermore, by performing Cox regression analysis, PCI was still associated with reduced long-term mortality (P=0.029, hazard ratio 0.5, 95% CI 0.3-0.9) after adjustment for PS and confounders: age, male sex, cognitive deterioration, uncured malignancies, left ventricular ejection fraction <45%, estimated glomerular filtration rate < 35 mL/min, ST-segment elevation myocardial infarction, mitral regurgitation, and medication at discharge with clopidogrel and statins. Conclusion: In octogenarians with ACS, PCI was associated with improved survival from all-cause death over 5 years of follow-up.
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| 4. |
- Decker, Ralph, 1968, et al.
(författare)
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GH dose reduction maintains normal prepubertal height velocity after initial catch up growth in short children.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:3, s. 835-844
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Tidskriftsartikel (refereegranskat)abstract
- GH responsiveness guides GH dosing during the catch-up growth (CUG) period; however, little is known regarding GH dosing during the prepubertal maintenance treatment period.To evaluate if standard deviation score (SDS) channel parallel growth with normal height velocity can be maintained following CUG by reducing GH dose by 50% in children receiving doses individualized based on estimated GH-responsiveness during the catch-up period.and settings: Prepubertal children (n=98; 72 boys) receiving GH during CUG (GH-deficient (n=33); non-GH-deficient (n=65)), were randomized after 2-3 years to either a 50% reduced individualized (GHRID; n=27; 20 boys) or unchanged individualized dose (GHUID; n=38; 27 boys). Another 33 children (25 boys) continued on a standard weight-based dose, 43 µg/kg/day (GHFIX).The primary endpoint was the proportion of children with ΔheightSDS within ±0.3 at 1 year after GH-dose reduction, versus two control groups: GHUID and GHFIX. The hypothesis was that heightSDS could be maintained within ±0.3 with a reduced individualized GH dose.For the intention-to-treat population at 1 year, 85% of the GHRIDgroup maintained ΔheightSDS within ±0.3 versus 41% in the GHUIDgroup, p=0.0055 and 48% in the GHFIXgroup, p=0.0047. ΔIGF-ISDS in the GHRIDgroup was (mean±SD) -0.75±1.0 at 3 months, p=0.003 and at 1 year -0.72±1.2, compared to the GHUIDgroup 0.15±1.2, p=0.005, and for the GHFIXgroup 0.05±1.0, p=0.02.Channel parallel growth, i.e. normal height velocity, and IGFSDS levels within ±2 were maintained after completed CUG using a 50% lower individualized dose than used during the CUG period.
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| 5. |
- Hagman, H., et al.
(författare)
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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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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:1, s. 140-147
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Tidskriftsartikel (refereegranskat)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. |
- Haraldsson, Inger, et al.
(författare)
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Prospective evaluation of coronary FLOW reserve and molecular biomarkers in patients with established coronary artery disease the PROFLOW-trial : Cross-sectional evaluation of coronary flow reserve
- 2019
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 15, s. 375-384
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI. Methods: PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 μg/kg/min). Independent predictors of CFR were assessed with multiple linear regression. Results: We included 619 patients. The median age was 69 (IQR 65–73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angio-tensin receptor blockers were independent predictors of CFR. Conclusion: In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.
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| 7. |
- Kotti, Angeliki, et al.
(författare)
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Survival benefit of statins in older patients with rectal cancer : A Swedish population-based cohort study
- 2019
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 10:5, s. 690-697
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIncreasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.Materials and MethodsThis study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.ResultsIn the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.ConclusionStatin use was related to improved survival in older patients with rectal cancer.This observation is important given the low cost and safety of statins as a drug.
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| 8. |
- Vernmark, Karolina, et al.
(författare)
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From palliative to curative treatment - stage IV mucinous adenocarcinoma, successfully treated with metronomic capecitabine in combination with Bevacizumab and surgery- a case report
- 2015
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Ingår i: BMC Cancer. - : BIOMED CENTRAL LTD. - 1471-2407. ; 15:884
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mucinous adenocarcinoma (MAC) represents 6-19 % of all colorectal carcinoma. It is associated with poorer response to chemotherapy and chemoradiotherapy. Case presentation: A 27-year-old Swedish woman presented with stomach pain and weight loss, and was diagnosed with locally advanced MAC in the transverse colon as well as 3 liver metastases. Neoadjuvant treatment with fluorouracil, folinic acid and oxaliplatin (FLOX) failed due to several infections, pulmonary embolism and deteriorated performance status. The patient was therefore considered palliative. Palliative treatment with metronomic capecitabine 500 mg x 2 daily and bevacizumab every other week were initiated. After 4 months of treatment the tumors had regressed and the patient was able to undergo radical surgery, thereby changing the treatment intention from palliative to curative. No adjuvant chemotherapy was given. There were no signs of recurrence 9 months later. Conclusions: The role of the combination of metronomic capecitabine and bevacizumab in patients with MAC merits further investigation.
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| 9. |
- Viketoft, Maria, et al.
(författare)
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Skadegörare och växtskydd i rot- och knölgrödor
- 2019
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Rapport (populärvet., debatt m.m.)abstract
- Det finns ett stort antal rot- och knölgrödor och många av dessa odlas på en liten areal i Sverige. Några håller på att introduceras (t.ex. sötpotatis) och kanske kan odlingen bli mer omfattande i framtiden. De flesta radodlade rot och knölgrödor har under en period i utvecklingen en stor yta av obeväxt mark som gynnar utvecklingen av ogräs och flera markbundna patogener/skadegörare, både svampar och skadedjur kan angripa flera av dessa grödor. Denna litteraturöversikt har arbetats fram inom ett fokusgrupp-projekt inom Plattform Växtskydd vid SLU 2017–2019.För att få en rimlig avgränsning valde vi att fokusera på de för närvarande större grödorna potatis, sockerbetor, lök och morot.Rapporten är indelad i tre delar som behandlar:• Insekter, virus och nematoder• Svampar, svampliknande organismer och bakterier• OgräsSyftet med fokusgruppen var att i samverkan mellan forskare, rådgivare och näring beskriva de viktigaste växtskyddsproblemen i rot- och knölgrödor samt att bidra till och försöka hitta vägar till att öka finansieringen till forskning för att underlätta innovation och genomförande av ett hållbart växtskydd i dessa grödor. Vi har lagt ett särskilt fokus på potatis, lök, morötter och sockerbetor.Några generella slutsatser om prioriterade forskningsområden:• Behovet av forskning utifrån ett odlingssystemperspektiv (växtföljd, odlingsåtgärder etc) där man kan undersöka flera skadegörare samtidigt. Att försöka få till fler projekt med deltagardriven forskning där odlare involveras och där odlarexperiment ingår.• Sjukdomar orsakade av svampen Rhizoctonia solani är generellt viktiga och skördeförlusterna orsakade av angrepp är dåligt kända i många fall och behöver utredas noggrannare. Svampen har ett brett spektrum av värdväxter, särskilt rot och knölgrödor och det finns interaktioner med flera andra skadegörare, t.ex. nematoder som är viktiga att studera vidare.• Viktigt att utreda konsekvenser och ta fram alternativa metoder till bekämpningsmedel som riskerar att försvinna och en förmodad framtida generellt minskad tillgång till effektiva kemiska medel.• Osäkerheten vad gäller ett framtida förbud för användning av glyfosat gör att utvecklingen av alternativa ogrässtrategier måste ges hög prioritet.• Stort behov av utveckling av alternativa bekämpningsmetoder och utveckling av appliceringsteknik anpassad till dessa.• Behov av teknisk utveckling kring prognosmodeller, sensor- och robotteknik för tidig detektion av olika skadegörare.• Behov av studier av skadegörares spridningsbiologi (vind-vektorer-maskin-utsäde).• Behov av bättre och säkrare diagnostikDet finns stort behov av ökad finansiering till den tillämpningsnära växtskyddsforskningen i samverkan med rådgivning och näring.
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| 10. |
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