| 1. |
- Cashin, Peter, 1984-, et al.
(författare)
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Peritoneal mesothelioma in Sweden : A population-based study
- 2019
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:14, s. 6468-6475
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Tidskriftsartikel (refereegranskat)abstract
- The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P =.04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P =.03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.
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| 2. |
- Chen, Dongfeng, et al.
(författare)
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RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children
- 2021
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 10:12, s. 3997-4003
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Tidskriftsartikel (refereegranskat)abstract
- B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be classified into subtypes according to the genetic aberrations they display. For instance, the translocation t(12;21)(p13;q22), representing the ETV6-RUNX1 fusion gene (ER), is present in a quarter of BCP-ALL cases. However, around 10% of the cases lack classifying chromosomal abnormalities (B-other). In pediatric ER BCP-ALL, rearrangement mediated by RAG (recombination-activating genes) has been proposed as the predominant driver of oncogenic rearrangement. Herein we analyzed almost 1600 pediatric BCP-ALL samples to determine which subtypes express RAG. We demonstrate that RAG1 mRNA levels are especially high in the ETV6-RUNX1 (ER) subtype and in a subset of B-other samples. We also define 31 genes that are co-expressed with RAG1 (RAG1-signature) in the ER subtype, a signature that also identifies this subset of B-other samples. Moreover, this subset also shares leukemia and pro-B gene expression signatures as well as high levels of the ETV6 target genes (BIRC7, WBP1L, CLIC5, ANGPTL2) with the ER subtype, indicating that these B-other cases are the recently identified ER-like subtype. We validated our results in a cohort where ER-like has been defined, which confirmed expression of the RAG1-signature in this recently described subtype. Taken together, our results demonstrate that the RAG1-signature identifies the ER-like subtype. As there are no definitive genetic markers to identify this novel subtype, the RAG1-signature represents a means to screen for this leukemia in children.
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| 3. |
- Cook, Daniel John, 1986, et al.
(författare)
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Molecular natural history of breast cancer: Leveraging transcriptomics to predict breast cancer progression and aggressiveness
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:10, s. 3551-3562
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Tidskriftsartikel (refereegranskat)abstract
- Cancer Medicine published by John Wiley & Sons Ltd. Background: Characterizing breast cancer progression and aggressiveness relies on categorical descriptions of tumor stage and grade. Interpreting these categorical descriptions is challenging because stage convolutes the size and spread of the tumor and no consensus exists to define high/low grade tumors. Methods: We address this challenge of heterogeneity in patient-specific cancer samples by adapting and applying several tools originally created for understanding heterogeneity and phenotype development in single cells (specifically, single-cell topological data analysis and Wanderlust) to create a continuous metric describing breast cancer progression using bulk RNA-seq samples from individual patient tumors. We also created a linear regression-based method to predict tumor aggressiveness in vivo from bulk RNA-seq data. Results: We found that breast cancer proceeds along three convergent phenotype trajectories: luminal, HER2-enriched, and basal-like. Furthermore, 31 296 genes (for luminal cancers), 17 827 genes (for HER2-enriched), and 18 505 genes (for basal-like) are dynamically differentially expressed during breast cancer progression. Across progression trajectories, our results show that expression of genes related to ADP-ribosylation decreased as tumors progressed (while PARP1 and PARP2 increased or remained stable), suggesting the potential for a differential response to PARP inhibitors based on cancer progression. Additionally, we developed a 132-gene expression regression equation to predict mitotic index and a 23-gene expression regression equation to predict growth rate from a single breast cancer biopsy. Conclusion: Our results suggest that breast cancer dynamically changes during disease progression, and growth rate of the cancer cells is associated with distinct transcriptional profiles.
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| 4. |
- Donati, Benedetta, et al.
(författare)
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Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.
- 2017
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Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 6:8, s. 1930-1940
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Tidskriftsartikel (refereegranskat)abstract
- In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P = 0.048) and healthy controls (P = 0.0006), independently of age and sex. We detected an enrichment of hTERT mutations in NAFLD-HCC, that was confirmed when we further considered a larger cohort of NAFLD-PLC, and was more marked in female patients (P = 0.03). No mutations were found in cirrhosis and local controls, and only one in 503 healthy Europeans from the 1000 Genomes Project (allelic frequency = 0.025 vs. <0.001; P = 0.0005). Mutations with predicted functional impact, including the frameshift Glu113Argfs*79 and missense Glu668Asp, cosegregated with liver disease in two families. Three patients carried missense mutations (Ala67Val in homozygosity, Pro193Leu and His296Pro in heterozygosity) in the N-terminal template-binding domain (P = 0.037 for specific enrichment). Besides Glu668Asp, the Ala67Val variant resulted in reduced intracellular protein levels. In conclusion, we detected an association between shorter telomeres in peripheral blood and rare germline hTERT mutations and NAFLD-HCC.
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| 5. |
- Garcia-Serrano, Ainhoa, et al.
(författare)
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Assessment of bacterial and viral gut communities in healthy and tumoral colorectal tissue using RNA and DNA deep sequencing
- 2023
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Ingår i: Cancer Medicine. - 2045-7634. ; 12:18, s. 19291-19300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) is known to present a distinct microbiome profile compared to healthy mucosa. Non-targeted deep-sequencing strategies enable nowadays full microbiome characterization up to species level. Aim: We aimed to analyze both bacterial and viral communities in CRC using these strategies. Materials & Methods: We analyzed bacterial and viral communities using both DNA and RNA deep-sequencing (Novaseq) in colorectal tissue specimens from 10 CRC patients and 10 matched control patients. Following taxonomy classification using Kraken 2, different metrics for alpha and beta diversities as well as relative and differential abundance were calculated to compare tumoral and healthy samples. Results: No viral differences were identified between tissue types, but bacterial species Polynucleobacter necessarius had a highly increased presence for DNA in tumors (p = 0.001). RNA analyses showed that bacterial species Arabia massiliensis had a highly decreased transcription in tumors (p = 0.002) while Fusobacterium nucleatum transcription was highly increased in tumors (p = 0.002). Discussion: Sequencing of both DNA and RNA enables a wider perspective of micriobiome profiles. Lack of RNA transcription (Polynucleobacter necessarius) casts doubt on possible role of a microorganism in CRC. The association of F. nucleatum mainly with transcription, may provide further insights on its role in CRC. Conclusion: Joint assessment of the metagenome (DNA) and the metatranscriptome (RNA) at the species level provided a huge coverage for both bacteria and virus and identifies differential specific bacterial species as tumor associated.
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| 6. |
- Kenne Sarenmalm, Elisabeth, et al.
(författare)
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Mindfulness and its efficacy for psychological and biological responses in women with breast cancer
- 2017
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 6:5, s. 1108-1122
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Tidskriftsartikel (refereegranskat)abstract
- Many breast cancer survivors have to deal with a variety of psychological and physiological sequelae including impaired immune responses. The primary purpose of this randomized controlled trial was to determine the efficacy of a mindfulness-based stress reduction (MBSR) intervention for mood disorders in women with breast cancer. Secondary outcomes were symptom experience, health status, coping capacity, mindfulness, posttraumatic growth, and immune status. This RTC assigned 166 women with breast cancer to one of three groups: MBSR (8 weekly group sessions of MBSR), active controls (self-instructing MBSR) and non-MBSR. The primary outcome measure was the Hospital Anxiety and Depression Scale. Secondary outcome measures were: Memorial Symptom Assessment Scale, SF-36, Sense of Coherence, Five Facets of Mindfulness Questionnaire, and Posttraumatic Growth Index. Blood samples were analyzed using flow cytometry for NK-cell activity (FANKIA) and lymphocyte phenotyping; concentrations of cytokines were determined in sera using commercial high sensitivity IL-6 and IL-8 ELISA (enzyme-linked immunosorbent assay) kits. Results provide evidence for beneficial effects of MBSR on psychological and biological responses. Women in the MBSR group experienced significant improvements in depression scores, with a mean pre-MBSR HAD-score of 4.3 and post-MBSR score of 3.3 (P = 0.001), and compared to non-MBSR (P = 0.015). Significant improvements on scores for distress, symptom burden, and mental health were also observed. Furthermore, MBSR facilitated coping capacity as well as mindfulness and posttraumatic growth. Significant benefits in immune response within the MBSR group and between groups were observed. MBSR have potential for alleviating depression, symptom experience, and for enhancing coping capacity, mindfulness and posttraumatic growth, which may improve breast cancer survivorship. MBSR also led to beneficial effect on immune function; the clinical implications of this finding merit further research.
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| 7. |
- Kristjansdottir, Björg, et al.
(författare)
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Early inflammatory response in epithelial ovarian tumor cyst fluids.
- 2014
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Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors.
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| 8. |
- Lönnerblad, Malin, 1970-, et al.
(författare)
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Occupational outcomes after high-grade or low-grade brain tumors in childhood: A Swedish, nationwide, registry-based study
- 2023
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 12:6, s. 7459-7469
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurvivors of pediatric brain tumors are at high risk of late complications that may affect their daily life in both short- and long-term perspectives. MethodsIn this nationwide registry-based study we explored the occupational outcomes, including employment, sickness or activity compensation and parental leave, in 452 individuals in Sweden, born 1988-1996, and diagnosed with a brain tumor before their 15th birthday. Their results were compared with 2188 matched controls. ResultsThere were significant differences between cases and controls for all assessed variables. The cases had benefitted from sickness or activity compensation 11 times more often than controls (CI 7.90-15.83; p < 0.001) between 2005 and 2016. Controls were almost three times more likely to have an employment (OR 0.36; CI 0.28-0.47; p < 0.001) and nearly twice as likely to have been on parental leave (OR 0.56; CI 0.39-0.80; p = 0.002). Although cases treated for high-grade tumors typically fared worse than those treated for low-grade tumors, significant differences for all assessed variables were also observed for cases treated for a low-grade tumor compared with controls. ConclusionsOur findings emphasize the need for follow-up programs for all brain tumor diagnoses, not only those known to be at most risk. This is evident, for example, from the high number of cases who received sickness or activity compensation.
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| 9. |
- Meijer, M., et al.
(författare)
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Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries
- 2018
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 7:1, s. 254-260
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Tidskriftsartikel (refereegranskat)abstract
- A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess the potential association between dispensed finasteride and MBC. A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual-level register data included country, dates of dispensed finasteride, MBC diagnosis, and death. Incidence rate ratios (IRRs) were estimated using a generalized linear model with a Poisson distribution. An increased risk of MBC was found among finasteride users (IRR=1.44, 95% confidence interval [95% CI]=1.11-1.88) compared to nonusers. The IRR increased to 1.60 (95% CI=1.20-2.13) when users in Norway and Sweden with short follow-up time were excluded. The highest IRR was seen among men with medium duration of dispensed finasteride, medium accumulated consumption of finasteride, and among men with first dispensed finasteride prescription 1-3years prior to diagnosis. The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and MBC. In conclusion, a significant association between dispensed finasteride and MBC was identified. However, due to limited data for adjustment of potential confounding and surveillance bias in the present study, further research is needed to confirm these results.
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| 10. |
- Noor Baloch, Adnan, et al.
(författare)
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The physical and psychological aspects of quality of life mediates the effect of radiation-induced urgency syndrome on disability pension in gynecological cancer survivors.
- 2023
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Ingår i: Cancer medicine. - 2045-7634. ; 12:16, s. 17377-17388
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Tidskriftsartikel (refereegranskat)abstract
- Radiation-induced fecal urgency syndrome is highly prevalent in gynecological cancer survivors. It is associated with decreased quality of life (QoL) and with disability pension. The literature remains unclear about the mediating role of physical and psychological aspects of QoL in the association between urgency syndrome and disability pension. Identifying the pathways between urgency syndrome and disability pension may help to create effective and timely interventions for increasing QoL and reducing disability pension among gynecological cancer survivors. We used patient-reported outcome measures from working-age gynecological cancer survivors (n = 247) and data on their disability pension from the official register. The mediating role of physical and psychological aspects of QoL was studied by utilizing mediation analysis based on the counterfactual framework, appropriate for binary outcome, binary mediator with an exposure-mediator interaction. The total effect (TE) was divided into direct and indirect effects using single mediation analysis. Adjusted relative risks and percentage mediated (95% confidence intervals) were calculated. All statistical tests were two-sided. Urgency syndrome increased the risk of disability pension both directly and indirectly (via QoL). Satisfaction with sleep mediated half of the TE (RR = 2.2 (1.1-4.1)) of urgency syndrome on disability pension. Physical health also mediated a similar proportion of the TE (RR = 2.1 (1.2-3.9)). The proportions mediated were higher for physical aspects of QoL (35%-71%) than for psychological aspects (2%-47%). The investigated aspects of the self-assessed QoL of gynecological cancer survivors may play a role in these women's continuing work-life. It appears that physical health, satisfaction with sleep, psychological well-being, and other investigated aspects of QoL mediate the urgency syndrome-disability pension association.
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