| 1. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 2. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 3. |
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| 4. |
- Danielsson, D., et al.
(författare)
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Brachytherapy and osteoradionecrosis in patients with base of tongue cancer
- 2023
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 143:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. Aims: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. Material and Methods: We used data from the Swedish Head and Neck Cancer Register between 2008–2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. Results: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p =.012), whereas overall survival did not differ (HR = 0.95, p =.782). Conclusions and Significance: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.
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| 5. |
- De Marchi, Tommaso, et al.
(författare)
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Proteogenomics decodes the evolution of human ipsilateral breast cancer
- 2023
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and proteome towards a highly replicating and genomically unstable IBTRs, possibly enhanced by APOBEC3B. In order to investigate the origins of IBTRs, a second analysis that included primaries with no recurrence pinpointed proliferation and immune infiltration as predictive of IBTR. In conclusion, our study shows that breast tumors evolve into different IBTRs depending on hormonal status and proliferation and that immune cell infiltration and Ki-67 are significantly elevated in primary tumors that develop IBTR. These results can serve as a starting point to explore markers to predict IBTR formation and stratify patients for adjuvant therapy.
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| 6. |
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| 7. |
- Neovius, Martin, et al.
(författare)
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Health Care Use During 20 Years Following Bariatric Surgery
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:11, s. 1132-1141
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Tidskriftsartikel (refereegranskat)abstract
- Context Bariatric surgery results in sustained weight loss; reduced incidence of diabetes, cardiovascular events, and cancer; and improved survival. The long-term effect on health care use is unknown. Objective To assess health care use over 20 years by obese patients treated conventionally or with bariatric surgery. Design, Setting, and Participants The Swedish Obese Subjects study is an ongoing, prospective, nonrandomized, controlled intervention study conducted in the Swedish health care system that included 2010 adults who underwent bariatric surgery and 2037 contemporaneously matched controls recruited between 1987 and 2001. Inclusion criteria were age 37 years to 60 years and body mass index of 34 or higher in men and 38 or higher in women. Exclusion criteria were identical in both groups. Interventions Of the surgery patients, 13% underwent gastric bypass, 19% gastric banding, and 68% vertical-banded gastroplasty. Controls received conventional obesity treatment. Main Outcome Measures Annual hospital days (follow-up years 1 to 20; data capture 1987-2009; median follow-up 15 years) and nonprimary care outpatient visits (years 2-20; data capture 2001-2009; median follow-up 9 years) were retrieved from the National Patient Register, and drug costs from the Prescribed Drug Register (years 7-20; data capture 2005-2011; median follow-up 6 years). Registry linkage was complete for more than 99% of patients (4044 of 4047). Mean differences were adjusted for baseline age, sex, smoking, diabetes status, body mass index, inclusion period, and (for the inpatient care analysis) hospital days the year before the index date. Results In the 20 years following their bariatric procedure, surgery patients used a total of 54 mean cumulative hospital days compared with 40 used by those in the control group (adjusted difference, 15; 95% CI, 2-27; P = .03). During the years 2 through 6, surgery patients had an accumulated annual mean of 1.7 hospital days vs 1.2 days among control patients (adjusted difference, 0.5; 95% CI, 0.2 to 0.7; P < .001). From year 7 to 20, both groups had a mean annual 1.8 hospital days (adjusted difference, 0.0; 95% CI, −0.3 to 0.3; P = .95). Surgery patients had a mean annual 1.3 nonprimary care outpatient visits during the years 2 through 6 vs 1.1 among the controls (adjusted difference, 0.3; 95% CI, 0.1 to 0.4; P = .003), but from year 7, the 2 groups did not differ (1.8 vs 1.9 mean annual visits; adjusted difference, −0.2; 95% CI, −0.4 to 0.1; P = .12). From year 7 to 20, the surgery group incurred a mean annual drug cost of US $930; the control patients, $1123 (adjusted difference, −$228; 95% CI, −$335 to −$121; P < .001). Conclusions Compared with controls, surgically treated patients used more inpatient and nonprimary outpatient care during the first 6-year period after undergoing bariatric surgery but not thereafter. Drug costs from years 7 through 20 were lower for surgery patients than for control patients.
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| 8. |
- Sjöström, Martin, et al.
(författare)
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Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant radiotherapy is the standard of care after breast-conserving surgery for primary breast cancer, despite a majority of patients being over- or under-treated. In contrast to adjuvant endocrine therapy and chemotherapy, no diagnostic tests are in clinical use that can stratify patients for adjuvant radiotherapy. This study presents the development and validation of a targeted gene expression assay to predict the risk of ipsilateral breast tumor recurrence and response to adjuvant radiotherapy after breast-conserving surgery in primary breast cancer. Methods: Fresh-frozen primary tumors from 336 patients radically (clear margins) operated on with breast-conserving surgery with or without radiotherapy were collected. Patients were split into a discovery cohort (N = 172) and a validation cohort (N = 164). Genes predicting ipsilateral breast tumor recurrence in an Illumina HT12 v4 whole transcriptome analysis were combined with genes identified in the literature (248 genes in total) to develop a targeted radiosensitivity assay on the Nanostring nCounter platform. Single-sample predictors for ipsilateral breast tumor recurrence based on a k-top scoring pairs algorithm were trained, stratified for estrogen receptor (ER) status and radiotherapy. Two previously published profiles, the radiosensitivity signature of Speers et al., and the 10-gene signature of Eschrich et al., were also included in the targeted panel. Results: Derived single-sample predictors were prognostic for ipsilateral breast tumor recurrence in radiotherapy-treated ER+ patients (AUC 0.67, p = 0.01), ER+ patients without radiotherapy (AUC = 0.89, p = 0.02), and radiotherapy-treated ER- patients (AUC = 0.78, p < 0.001). Among ER+ patients, radiotherapy had an excellent effect on tumors classified as radiosensitive (p < 0.001), while radiotherapy had no effect on tumors classified as radioresistant (p = 0.36) and there was a high risk of ipsilateral breast tumor recurrence (55% at 10 years). Our single-sample predictors developed in ER+ tumors and the radiosensitivity signature correlated with proliferation, while single-sample predictors developed in ER- tumors correlated with immune response. The 10-gene signature negatively correlated with both proliferation and immune response. Conclusions: Our targeted single-sample predictors were prognostic for ipsilateral breast tumor recurrence and have the potential to stratify patients for adjuvant radiotherapy. The correlation of models with biology may explain the different performance in subgroups of breast cancer.
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| 9. |
- Sjöström, Martin, et al.
(författare)
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Lack of G protein-coupled estrogen receptor (GPER) in the plasma membrane is associated with excellent long-term prognosis in breast cancer
- 2014
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Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 145:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled estrogen receptor (GPER), or GPR30, is a membrane receptor reported to mediate non-genomic estrogen responses. Tamoxifen is a partial agonist at GPER in vitro. Here, we investigated if GPER expression is prognostic in primary breast cancer, if the receptor is treatment-predictive for adjuvant tamoxifen, and if receptor subcellular localization has any impact on the prognostic value. Total and plasma membrane (PM) GPER expression was analyzed by immunohistochemistry in breast tumors from 742 postmenopausal lymph node-negative patients subsequently randomized for tamoxifen treatment for 2-5 years versus no systemic treatment, regardless of estrogen receptor (ER) status, and with a median follow-up of 17 years for patients free of event. PM GPER expression was a strong independent prognostic factor for poor prognosis in breast cancer without treatment-predictive information for tamoxifen. In the tamoxifen-treated ER-positive and progesterone receptor (PgR)-positive patient subgroup, the absence of PM GPER (53 % of all ER-positive tumors) predicted 91 % 20-year distant disease-free survival, compared to 73 % in the presence of GPER (p = 0.001). Total GPER expression showed positive correlations with ER and PgR and negative correlation with histological grade, but the correlations were biphasic. On the other hand, PM GPER expression showed strong negative correlations with ER and PgR, and strong positive correlation with HER2 overexpression and high histological grade. GPER overexpression and PM localization are critical events in breast cancer progression, and lack of GPER in the PM is associated with excellent long-term prognosis in ER-positive and PgR-positive tamoxifen-treated primary breast cancer.
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| 10. |
- Sjöström, Mats, et al.
(författare)
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Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Background: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien–Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien–Dindo grade IIIa–V events was significantly lower for patients treated with primary closure without grafts. Significance: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
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