| 10901. |
- Kinhult, Sara, et al.
(författare)
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Regional variation in usage of TTF (Optune) Regional variation i användningen av TTF vid glioblastombehandling : [Regional variation in usage of TTF (Optune)]
- 2023
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Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.
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| 10902. |
- Kinos, Sampsa, et al.
(författare)
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Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 248-258
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study.Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients.Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs.Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.
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| 10903. |
- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 10904. |
- Kirik, Ufuk
(författare)
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Development of Computational Methods for Cancer Research: Strategies for closing the feedback loop in omics workflows
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As the ultimate workhorses of the living things, proteins undergo significant regulatory activity throughout the lifetime of a cell or an organism. Many complex diseases effect the protein composition, expression or modification in the cells or tissues they arise in. It is then no surprise that proteomics is a field full of promise, one which is expected to generate significant insights towards functional characterization of cancer and deliver potential targets of diagnostic, prognostic or therapeutic value. It is also a science in its teens, which still grows and keeps changing as it grows with the technological advances in instrumentation as the driving force. Since data analysis routines are yet to be established fully, functional characterization of protein expression regulation in cancer remains an open question. The work presented in this thesis provides an overview of the field based on technological, computational and biological aspects in the introductory chapters, introduces a novel method for functional evaluation of changes in protein expression and demonstrates its utility in PAPER I, and describes the insights gained from investigating proteomes of several different types of human malignancies. PAPER I underlines the challenges in functional analysis of expression data, especially from LC-MS/MS experiments, and describes a method based on a relatively simple mathematical model, which is used for subsequent analyses. PAPER II describes a study on soft-tissue sarcomas, with the proteomic analysis revealing insights to protein expression patterns potential differentiation paths. PAPER III demonstrates a pairwise comparison of malignancies of gastroesophageal track and corresponding normal tissue; we highlight several proteins and pathways as likely targets of expression regulation. PAPER IV and V on the other hand focus on breast cancer. PAPER IV presents results from an investigation of immortalized breast cancer cell lines and raises the question of how well these model systems represents the tumours they are expected to be alike. PAPER V demonstrates the therapeutic potential of inhibiting oestrogen signalling in ER+ breast cancer, using a luminal type patient-derived xenograft mouse model. Collectively, this thesis presents some of the key concepts in quantitative proteomics workflows, elaborates on the importance of data processing routines and through the papers in the appendix demonstrates the potential of functional analysis algorithms in generating insights to cancer biology.
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| 10905. |
- Kirik, Ufuk, et al.
(författare)
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Discovery-based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas.
- 2014
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 12:12, s. 1729-1739
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathological and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human softtissue sarcomas, including subtype heterogeneity, using 2D-gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach and identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biological nodes like apoptosis, cytoskeleton remodeling and telomere regulation are differentially regulated among these subgroups. Finally, investigating the Kirik et al. Protein profiling of leiomyosarcoma Page 2 of 24 similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison to pleomorphic leiomyosarcomas. Implications: These results suggest that UPS tumors share a similar lineage as leiomyosarcomas, and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells.
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| 10906. |
- Kirstetter, Peggy, et al.
(författare)
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Modeling of C/EBP alpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells
- 2008
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 13:4, s. 299-310
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBP alpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1(+)c-Kit(+) population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1(+)c-Kit(+) progenitors revealed a signature shared with MLL-AF9-transformed AML.
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| 10907. |
- Kirti, Apoorv, et al.
(författare)
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Nanoparticle-mediated metronomic chemotherapy in cancer : A paradigm of precision and persistence
- 2024
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Ingår i: Cancer Letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 594
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Tidskriftsartikel (refereegranskat)abstract
- Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.
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| 10908. |
- Kiss, Eszter, et al.
(författare)
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Granulosa cell tumors in girls : Preliminary results of a meta-analysis of new and published cases
- 2023
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 96:Suppl. 4, s. 126-127
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Granulosa cell tumors (GCT) originate from sex cord/stromal tissue in the gonad. They are typically located in an ovary, but extra-gonadal localisation exists. These tumors are extremely rare in children and no systematic review has been published. The objective of this systematic review is to examine the following questions: What is the clinical picture of girls with a GCT? How are these patients treated and what is their prognosis?Methods: To be included in the review, the article had to present a new case with GCT fulfilling the following criteria: female human fetus or a girl aged < 19 years with clinical information included a tumor containing granulosa cells.The databases MEDLINE, Embase, Web of Science, and CINAHL were searched in November 2021. To find new cases, we asked pediatric endocrinologists in Sweden to report patients after informed consent had been secured. We also collected data from a Swedish paediatric reference pathology laboratory.Results: The search identified 1,894 published references of which 35 were duplicates. We have screened 1,859 abstracts. We are in the process of reading 824 selected articles in full text to check for eligibility. Individual participant data has been extractedfrom 20 of the published reports for preliminary results. Nineteen new Swedish cases with a GCT were identified.The preliminary analysis of 39 patients’ data shows an average age of 7.3 years at the time of diagnosis (range: antenatal diagnosis up to 18 years of age). Symptoms at presentation were: prepubertal breast enlargement, vaginal discharge/bleeding, abdominal distension or pain, pubic hair growth, fever, constipation, swelling of vulva or cliteromegaly, hyperpigmentation of the skin, primary/secondary amenorrhea, headache, hirsutism and advanced linear growth.The histopathological diagnosis was juvenile GCT in 76.9%, adult GCT in 12.8%, a mixed type of juvenile and adult GCT in 7.7% and another type of tumor containing granulosa cell component in 2.6% of the cases.All patients received surgical treatment except one with a post-mortem GCT diagnoses. Adjuvant chemotherapy was administered in two cases.Three patients (7.7%) died, two of them due to late discovery of the primary tumor and one secondary to local recurrence of the tumor with metastases 4 years after the primary diagnosis.Conclusion: GCT can present in all pediatric ages and often, but far from always, with endocrine symptoms such as peripheral precautious puberty. Data from this systematic review will hopefully promote early recognition of this malignant disease.
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| 10909. |
- Kiss, Nicole, et al.
(författare)
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Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.
- 2020
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Ingår i: Current osteoporosis reports. - : Springer Science and Business Media LLC. - 1544-2241 .- 1544-1873. ; 18:3, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer.RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.
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| 10910. |
- Kitahara, Cari M., et al.
(författare)
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Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
- 2016
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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