| 51. |
- Hofving, Tobias, 1989, et al.
(författare)
-
177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition
- 2019
-
Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 26:4, s. 437-449
-
Tidskriftsartikel (refereegranskat)abstract
- Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.
|
|
| 52. |
- Ge, Chenjie, 1991, et al.
(författare)
-
Cross-Modality Augmentation of Brain Mr Images Using a Novel Pairwise Generative Adversarial Network for Enhanced Glioma Classification
- 2019
-
Ingår i: Proceedings - International Conference on Image Processing, ICIP. - 1522-4880.
-
Konferensbidrag (refereegranskat)abstract
- © 2019 IEEE. Brain Magnetic Resonance Images (MRIs) are commonly used for tumor diagnosis. Machine learning for brain tumor characterization often uses MRIs from many modalities (e.g., T1-MRI, Enhanced-T1-MRI, T2-MRI and FLAIR). This paper tackles two issues that may impact brain tumor characterization performance from deep learning: insufficiently large training dataset, and incomplete collection of MRIs from different modalities. We propose a novel pairwise generative adversarial network (GAN) architecture for generating synthetic brain MRIs in missing modalities by using existing MRIs in other modalities. By improving the training dataset, we aim to mitigate the overfitting and improve the deep learning performance. Main contributions of the paper include: (a) propose a pairwise generative adversarial network (GAN) for brain image augmentation via cross-modality image generation; (b) propose a training strategy to enhance the glioma classification performance, where GAN-augmented images are used for pre-training, followed by refined-training using real brain MRIs; (c) demonstrate the proposed method through tests and comparisons of glioma classifiers that are trained from mixing real and GAN synthetic data, as well as from real data only. Experiments were conducted on an open TCGA dataset, containing 167 subjects for classifying IDH genotypes (mutation or wild-type). Test results from two experimental settings have both provided supports to the proposed method, where glioma classification performance has consistently improved by using mixed real and augmented data (test accuracy 81.03%, with 2.57% improvement).
|
|
| 53. |
- Wennergren, Göran, 1947
(författare)
-
Medicinarminnen som fängslar
- 2019
-
Ingår i: Läkartidningen. - 0023-7205. ; 116
-
Recension (övrigt vetenskapligt/konstnärligt)
|
|
| 54. |
- Gulyas, Miklos, et al.
(författare)
-
COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.
- 2018
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 244-250
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.
|
|
| 55. |
- Hammarsten, Jan, et al.
(författare)
-
A stage-dependent link between metabolic syndrome components and incident prostate cancer
- 2018
-
Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 15:5, s. 321-333
-
Forskningsöversikt (refereegranskat)abstract
- Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
|
|
| 56. |
- Troisi, R., et al.
(författare)
-
The role of pregnancy, perinatal factors and hormones in maternal cancer risk : a review of the evidence
- 2018
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:5, s. 430-445
-
Tidskriftsartikel (refereegranskat)abstract
- An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy related exposures influence foetal growth cell division and organ functioning and may have a longlasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.
|
|
| 57. |
- Bock, David, 1976, et al.
(författare)
-
Habits and self-assessed quality of life, negative intrusive thoughts and depressed mood in patients with prostate cancer: a longitudinal study
- 2017
-
Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:5, s. 353-359
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate the association of self-assessed preoperative physical activity, alcohol consumption and smoking with self-assessed quality of life, negative intrusive thoughts and depressed mood after radical prostatectomy.Materials and methods: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, controlled, non-randomized longitudinal trial of patients (n=4003) undergoing radical prostatectomy at 14 centers in Sweden. Validated patient questionnaires were collected at baseline, and 3, 12 and 24 months after surgery.Results: Preoperative medium or high physical activity or low alcohol consumption or non-smoking was associated with a lower risk of depressed mood. High alcohol consumption was associated with increased risk of negative intrusive thoughts. Postoperatively, quality of life and negative intrusive thoughts improved gradually in all groups. Depressed mood appeared to be relatively unaffected.Conclusions: Evaluation of preoperative physical activity, tobacco and alcohol consumption habits can be used to identify patients with a depressed mood in need of psychological support before and immediately after surgery. Quality of life and intrusive thoughts improved postoperatively.
|
|
| 58. |
- Bock, David, 1976, et al.
(författare)
-
Agreement between patient reported outcomes and clinical reports after radical prostatectomy - a prospective longitudinal study
- 2019
-
Ingår i: Bmc Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn clinical research information can be retrieved through various sources. The aim is to evaluate the agreement between answers in patient questionnaires and clinical reports in a study of patients after radical prostatectomy and patient characteristics associated with agreement between these two data sources.MethodsIn the prospective non-randomized longitudinal trial LAParoscopic Prostatectomy Robot Open (LAPPRO) 4003 patients undergoing radical prostatectomy at 14 centers in Sweden were followed. Analysis of agreement is made using a variety of methods, including the recently proposed Gwet's AC1, which enables us to handle the limitations of Cohen's Kappa where agreement depends on the underlying prevalence.ResultsThe incidence of postoperative events was consistently reported higher by the patient compared with the clinical reports for all outcomes. Agreement regarding the absence of events (negative agreement) was consistently higher than agreement regarding events (positive agreement) for all outcome variables. Overall impression of agreement depends on which measure used for the assessment. The previously reported desirable properties of Gwet's AC1 as well as the patient characteristics associated with agreement were confirmed.ConclusionThe differences in incidence and agreement across the different variables and time points highlight the importance of carefully assessing which source of information to use in clinical research.
|
|
| 59. |
- Ljungman, Lisa, et al.
(författare)
-
Sexual dysfunction and reproductive concerns in young women with breast cancer : Type, prevalence, and predictors of problems
- 2018
-
Ingår i: Psycho-Oncology. - : John Wiley & Sons. - 1057-9249 .- 1099-1611. ; 27, s. S128-S128
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A dearth of studies focusing on young women (<40 years) with breast cancer have hampered the understanding of the type, prevalence, and predictors of sexual dysfunction and reproductive concerns in this population.METHODS: Data were collected from 181 women (response rate = 60%) diagnosed with breast cancer approximately 2 years previously (age 21-39) using the Swedish National Quality Registry for Breast Cancer and a survey including standardized measures of sexual dysfunction, reproductive concerns, body image, and health-related quality of life. Multivariable logistic binary regression analyses were used to identify predictors of sexual dysfunction and reproductive concerns.RESULTS: Sexual dysfunction in at least one domain was reported by 68% of the women, and a high level of reproductive concerns in at least one dimension was reported by 58%. Model results showed that current endocrine treatment was a significant predictor of dysfunction related to lubrication (OR 3.8, 95% CI 1.2-12.1) and vaginal discomfort (OR 8.7, 95% CI 1.5-51.5). Negative body image was related to satisfaction with sex life (OR 1.1, 95% CI 1.0-1.2). A high level of reproductive concerns was predicted by a wish for (additional) children in the future (OR 3.4, 95% CI 1.1-10.2) and by previous chemotherapy (OR 2.5, 95% CI 1.1-5.9).CONCLUSIONS: Sexual dysfunction and reproductive concerns are common in young women with breast cancer. Current endocrine treatment, previous chemotherapy, a negative body image, and a wish for children in the future predict higher level of problems.
|
|
| 60. |
|
|
