| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Adnan, Ali, et al.
(författare)
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Health-related quality of life among tonsillar carcinoma patients in Sweden in relation to treatment and comparison with quality of life among the population
- 2020
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:5, s. 860-872
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Tidskriftsartikel (refereegranskat)abstract
- Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.
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| 3. |
- Adrian, Gabriel, et al.
(författare)
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Altered fractionation diminishes importance of tumor volume in oropharyngeal cancer : Subgroup analysis of ARTSCAN-trial
- 2020
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Ingår i: Head and Neck. - : Wiley-Blackwell. - 1043-3074 .- 1097-0347. ; 42:8, s. 2099-2105
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Tidskriftsartikel (refereegranskat)abstract
- Background: A large tumor volume negatively impacts the outcome of radiation therapy (RT). Altered fractionation (AF) can improve local control (LC) compared with conventional fractionation (CF). The aim of the present study was to investigate if response to AF differs with tumor volume in oropharyngeal cancer.Methods: Three hundred and twenty four patients with oropharyngeal cancer treated in a randomized, phase III trial comparing CF (2 Gy/d, 5 d/wk, 7 weeks, total dose 68 Gy) to AF (1.1 Gy + 2 Gy/d, 5 d/wk, 4.5 weeks, total dose 68 Gy) were analyzed.Results: Tumor volume had less impact on LC for patients treated with AF. There was an interaction between tumor volume and fractionation schedule (P = .039). This differential response was in favor of CF for small tumors and of AF for large tumors.Conclusion: AF diminishes the importance of tumor volume for local tumor control in oropharyngeal cancer.
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| 4. |
- Adrian, Gabriel, et al.
(författare)
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Circulating tumour HPV16 DNA quantification – A prognostic tool for progression-free survival in patients with HPV-related oropharyngeal carcinoma receiving curative chemoradiotherapy
- 2023
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Ingår i: Radiotherapy and Oncology. - 0167-8140. ; 186
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Circulating tumour (ct) human papillomavirus (HPV) DNA is detectable in HPV-related oropharyngeal carcinoma (OPSCC) patients and has the potential to become an important clinical tool. This study aimed to evaluate the prognostic significance of ctHPV16-DNA kinetics during treatment with chemoradiotherapy in HPV-related OPSCC. Patients with p16-positive OPSCC recruited to the ARTSCAN III trial, comparing radiotherapy plus cisplatin with radiotherapy plus cetuximab, constituted the study cohort. Materials and methods: Blood samples before start and at the end of treatment of 136 patients were analysed. ctHPV16-DNA was quantified by real-time (q)PCR. The correlation between ctHPV16-DNA levels and tumour burden was investigated with Pearson regression analysis. The prognostic value of ctHPV16-DNA levels at baseline and decline during treatment was evaluated by area-under-the-curve (AUC) calculations and analysed with univariable and multivariable Cox proportional hazards models. Results: ctHPV16-DNA was detectable with qPCR in 108/136 patients before start of treatment and cleared in 74% of these patients at the end of treatment. Disease burden was significantly correlated with baseline ctHPV16-DNA levels (R = 0.39, p=<0.001). Both lower baseline levels and AUC-ctHPV16DNA were associated with improved progression-free survival (p = 0.01 and p < 0.001), overall survival (p = 0.013 and p = 0.002), but not local tumour control (p = 0.12 and p = 0.2, respectively), with a stronger association for AUC-ctHPV16DNA (likelihood ratio test 10.5 vs 6.5 in Cox regression analyses of progression-free survival). In multivariable analysis including tumour volume (GTV-T) and treatment allocation (cisplatin vs cetuximab), AUC-ctHPV16DNA remained a significant prognostic marker of progression-free survival. Conclusion: ctHPV16-DNA is an independent prognostic factor in HPV-related OPSCC.
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| 5. |
- Adrian, Gabriel, et al.
(författare)
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Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors
- 2023
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:11, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Analyses of clinical outcomes following radiotherapy (RT) have advanced our understanding of fundamental radiobiological characteristics in head and neck squamous cell carcinoma (HNSCC). Low fractionation sensitivity appears to be a common feature, as well as susceptibility to changes in overall treatment time (OTT). Large tumors should be harder to cure if a successful RT requires the sterilization of all clonogenic cells. Congruently, primary tumor volume has proven to be an important parameter. However, most findings come from an era when p16-negative HNSCC was the dominant tumor type. HPV-associated, p16-positive, oropharyngeal tumors (OPSCC) are more radiosensitive and have better outcome. The current study aims to investigate the role of primary tumor volume, OTT and estimate α/β-ratio for p16-positive OPSCC, and to quantify the differences in radiosensitivity depending on p16-status.METHODS: A cohort of 523 patients treated with RT was studied using a tumor control probability (TCP)-model that incorporates primary tumor volume (V) raised to an exponent c, OTT and α/β-estimation. The significance of V was also investigated in Cox-regression models.RESULTS: In the p16-positive cohort (n = 433), the volume exponent c was 1.44 (95%CI 1.06-1.91), compared to 0.90 (0.54-1.32) for p16-negative tumors (n = 90). Hazard ratios per tumor volume doubling were 2.37 (1.72-3.28) and 1.83 (1.28-2.62) for p16-positive and p16-negative, respectively. The estimated α/β-ratio was 9.7 Gy (-2.3-21.6), and a non-significant daily loss of 0.30 Gy (-0.17-0.92) was found. An additional dose of 6.8 Gy (interquartile range 4.8-9.1) may theoretically counteract the more radioresistant behavior of p16-negative tumors.CONCLUSION: Primary tumor volume plays a crucial role in predicting local tumor response, particularly in p16-positive OPSCC. The estimated α/β-ratio for p16-positive oropharyngeal tumors aligns with previous HNSCC studies, whereas the impact of prolonged OTT was slightly less than previously reported. The differences in radiosensitivity depending on p16-status were quantified. The findings should be validated in independent cohorts.
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| 6. |
- Adrian, Gabriel, et al.
(författare)
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Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy
- 2022
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Ingår i: Radiation Oncology. - : Springer Nature. - 1748-717X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT). Methods: Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume. Results: The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume. Conclusions: Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.
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| 7. |
- Berg, Malin, 1976, et al.
(författare)
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A national study of health-related quality of life in patients with cancer of the base of the tongue compared to the general population and to patients with tonsillar carcinoma
- 2021
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 43:12, s. 3843-3856
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Tidskriftsartikel (refereegranskat)abstract
- Background This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT). Methods CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients. Results The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems. Conclusion One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.
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| 8. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 9. |
- Gebre-Medhin, Maria, et al.
(författare)
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Dose-volume analysis of radiation-induced trismus in head and neck cancer patients
- 2016
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Ingår i: Acta Oncologica. - 0284-186X. ; 55:11, s. 1313-1317
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Trismus is a treatment-related late side effect in patients treated for cancer in the head and neck region (HNC). The condition can have a considerable negative impact on nutrition, dental hygiene, ability to speak and quality of life. We have previously studied trismus within the frame of a randomized phase 3 study of HNC patients treated with mainly three-dimensional (3D) conformal radiotherapy (CRT) and found a strong association to mean radiation dose to the mastication muscles, especially the ipsilateral masseter muscle (iMAS). In the present study we have investigated trismus prevalence and risk factors in a more recent cohort of patients, treated with todays’ more updated radiation techniques. Material and methods: Maximal interincisal distance (MID) was measured on 139 consecutive patients. Trismus was defined as MID ≤35 mm. Patient-, disease- and treatment-specific data were retrospectively recorded. Differences between groups were analyzed and mean absorbed dose to mastication structures was evaluated. Dosimetric comparisons were made between this study and our previous results. Results: The prevalence of trismus was 24% at a median of 16 months after completion of radiotherapy. In bivariate analysis treatment technique (3DCRT vs. intensity modulated radiotherapy or helical tomotherapy), tumor site (oropharynx vs. other sites) and mean radiation doses to the ipsilateral lateral pterygoid muscle, the paired masseter muscles and the iMAS were significantly associated with MID ≤35 mm. In multivariable analysis only mean radiation dose to the iMAS was significantly associated to MID ≤35 mm. Conclusion: Mean radiation dose to the ipsilateral masseter muscle is an important risk factor for trismus development. Dose reduction to this structure during radiotherapy should have a potential to diminish the prevalence of trismus in this patient group.
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| 10. |
- Gebre-Medhin, Maria, 1965
(författare)
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Prolactin and growth hormone in breast cancer. Studies of human breast cancer and transgenic tumor models
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prolactin (PRL) and growth hormone (GH) are two related pituitary peptide hormones of importance during normal mammary gland development. Furthermore, their involvement in development and growth of malignant mammary tumors has been suggested by several investigators. By producing rat PRL transgenic (rPRL) mice and bovine GH transgenic (bGH) mice it was shown that activation of the PRL receptor (PRLR) but not the GH receptor (GHR) is important for mammary tumor development in mice. Mammary explant organ culture studies suggest a functional role of rPRL locally produced in the mammary gland.Studies of rPRL mammary glands with different degrees of hyperplasia showed that the percentage of estrogen receptor a (ERa)-expressing epithelial cells was markedly increased in severely hyperplastic rPRL mammary glands. Plasma levels of 17ß-estradiol, estimated over a 34-day period of time were increased in rPRL mice, while progesterone levels were unchanged compared to control animals. Together these data suggest a role of increased ERa activation during mammary tumor development in rPRL mice. It was also shown that insulin-like growth factor (IGF)-I receptor (IGF-IR) activation is important for rPRL mammary tumor cell growth in vitro, while mRNA expression levels of IGF-I, IGF-II and IGF-IR in rPRL mammary glands do not increase during the course of mammary tumor development.GHR expression was studied in human breast cancer specimens, and it was found that nearly all tumors analyzed expressed GHR. By immunohistochemical studies and by western blot analyses it was found that GHR expression was increased in most tumor tissues compared to adjacent normal mammary tissues.
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| 11. |
- Gebre-Medhin, Samuel, et al.
(författare)
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Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors.
- 2012
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 181:3, s. 1069-1077
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Tidskriftsartikel (refereegranskat)abstract
- Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor of unknown lineage. Although most cases are histologically and clinically benign, some show malignant morphological features and local recurrences are not uncommon; a few may even metastasize. In the present study, cytogenetic analysis identified different structural rearrangements of chromosome band 6p21 in tumor cells from three cases of OFMT, including one with typical, one with atypical, and one with malignant morphological features. Mapping of the 6p21 breakpoint by fluorescence in situ hybridization (FISH) indicated that the PHF1 gene was rearranged in all three cases. Further FISH, 5'-rapid amplification of cDNA ends, and RT-PCR analyses disclosed an EP400/PHF1 fusion transcript in one of the cases. Interphase FISH on tumor sections from 13 additional cases of OFMT showed rearrangement of the PHF1 locus in four of four typical, two of three atypical, and one of six malignant lesions. Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions. The PHF1 protein interacts with the polycomb-repressive complex 2 (PRC2), which, in turn, regulates the expression of a variety of developmental genes. Thus, the results indicate that deregulation of PRC2 target genes is crucial for OFMT development.
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| 12. |
- Gustafsson, Jan, et al.
(författare)
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APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:24, s. 2096-2103
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.
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| 13. |
- Hildingsson, Sofia, et al.
(författare)
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Hypoxia in relationship to tumor volume using hypoxia PET-imaging in head & neck cancer – A scoping review
- 2022
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 40-46
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Forskningsöversikt (refereegranskat)abstract
- Background: Hypoxia and large tumor volumes are negative prognostic factors for patients with head and neck squamous cell carcinoma (HNSCC) treated with radiation therapy (RT). PET-scanning with specific hypoxia-tracers (hypoxia-PET) can be used to non-invasively assess hypoxic tumor volume. Primary tumor volume is readily available for patients undergoing RT. However, the relationship between hypoxic volume and primary tumor volume is yet an open question. The current study investigates the hypotheses that larger tumors contain both a larger hypoxic volume and a higher hypoxic fraction. Methods: PubMed and Embase were systematically searched to identify articles fulfilling the predefined criteria. Individual tumor data (primary tumor volume and hypoxic volume/fraction) was extracted. Relationship between hypoxic volume and primary tumor volume was investigated by linear regression. The correlation between hypoxic fraction and log2(primary tumor volume) was determined for each cohort and in a pooled analysis individual regression slopes and coefficients of determination (R2) were weighted according to cohort size. Results: 21 relevant articles were identified and individual data from 367 patients was extracted, out of which 323 patients from 17 studies had quantifiable volumes of interest. A correlation between primary tumor volume and PET-determined hypoxic volume was found (P <.001, R2 = 0.46). Larger tumors had a significantly higher fraction of hypoxia compared with smaller tumors (P<.01). The weighted analysis of all studies revealed that for each doubling of the tumor volume, the hypoxic fraction increased by four percentage points. Conclusion: This study shows correlations between primary tumor volume and hypoxic volume as well as primary tumor volume and the hypoxic fraction in patients with HNSCC. The findings suggest that not only do large tumors contain more cancer cells, they also have a higher proportion of potentially radioresistant hypoxic cells. This knowledge can be important when individualizing RT.
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| 14. |
- Lindgren, Gustaf, et al.
(författare)
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Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
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| 15. |
- Ling, Charlotte, et al.
(författare)
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Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice
- 2000
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Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 141:10, s. 3564-3572
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Tidskriftsartikel (refereegranskat)abstract
- There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRL-transgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.
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| 16. |
- Palat, Gayatri, et al.
(författare)
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The introduction and experiences of methadone for treatment of cancer pain at a low-resource governmental cancer center in india
- 2021
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Ingår i: Indian Journal of Palliative Care. - 0973-1075. ; 27:3, s. 382-404
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to describe the clinical experience of the health-care professionals (HCPs) responsible for the introduction of methadone, for the treatment of complex cancer pain, at a low-resource hospital in India in a patient-group, burdened by illiteracy, and low socio-economic status. Materials and Methods: Ten HCPs: Four medical doctors, four nurses, one pharmacist, and one hospital administrator were interviewed. The interviews are examined using a qualitative conventional content analysis. Results: The interviews showed a confidence amongst the HCPs, responsible for the safe introduction of methadone in a stressful and low-resource surrounding, to patients with cancer pain and the different aspects of methadone, as initiation, titration, and maintenance of treatment. Conclusion: Introduction of methadone for cancer pain management is safe and feasible although low resources in a challenging hospital setting and care environment.
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| 17. |
- Palat, Gayatri, et al.
(författare)
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The use of Methadone in adult patients with cancer-pain at a governmental cancer centre in India
- 2021
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Ingår i: Indian Journal of Palliative Care. - 0973-1075. ; 27:1, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- Background: Management of cancer-related pain relies on the access to opioids. When regular opioids as morphine are not tolerated or are insufficient, adjuvant opioids as methadone are an affordable and effective analgesic. Aim: The aim of the project was to describe the pattern of use and clinical experiences of methadone in patients with cancer-related pain at a low-resource hospital in Hyderabad, one of few Indian cancer centers with permission to prescribe methadone. Methods: Medical records of all patients who had been prescribed methadone, September 9, 2017 and November 19, 2019 were studied retrospectively. Data on analgesic treatment and opioid side effects were analyzed. Results: A total of 93 adult cancer patients were included in the study. A majority of patients (79%) were prescribed opioid analgesic, mainly morphine, before methadone introduction. The initial daily dose of methadone ranged between 5 and 22.5 years and in the vast majority of the patients 5 mg, divided in two daily administrations. A good analgesic effect, with decreased pain, was reported in 60% of the patients. No severe side effects were reported. Conclusions: In this study, methadone as a primary opioid was used with a good analgesic effect for cancer pain in a low-resource setting. Indication for methadone was mainly uncontrolled pain with a regular opioid treatment. No severe adverse effects were reported. Further research and prospective studies are needed on methadone treatment in low-resource settings to establish the robust guidelines to support prescribing physicians.
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| 18. |
- Palat, Gayatri, et al.
(författare)
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The use of methadone in pediatric cancer pain - a retrospective study from a governmental cancer center in India
- 2021
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Ingår i: Indian Journal of Palliative Care. - 0973-1075. ; 27:1, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: The management of cancer-related pain relies on access to opioids. When regular opioids are not tolerated, or are insufficient, methadone is an affordable and effective analgesic. Aim: The aim of the project was to describe the pattern of use and clinical experience of methadone in pediatric cancer pain at a governmental cancer hospital in Hyderabad, one of the four Indian cancer centers with permission to prescribe methadone. Methods: This was a retrospective study of medical records of all children, under the age of 18, who had been prescribed methadone from September 9, 2017, to November 19, 2019. Data on analgesic effect, prior and concomitant analgesic treatment, opioid side effects, and the handling of methadone were analyzed. Results: A total of 11 children were identified and studied. Methadone was introduced mainly when pain was uncontrolled by regular opioids. Initial daily doses ranged from 1 to 15 mg. The duration of treatment ranged from 7 to 307, with a median of 50 days in the nine patients where treatment exceeded one single dosage. Good analgesic effect was reported in 5/9 children, unchanged from previous analgesic treatment in three patients and without any effect in one child. No severe side effects were reported. Conclusion: Low-dose methadone in the treatment of pediatric cancer pain at a low-resource cancer center was safe and well tolerated by the patients, with long treatment durations. It was safely managed, administered with single to double daily dosages, hence easy for patients and family to handle, and an affordable treatment option.
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| 19. |
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| 20. |
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| 21. |
- Söderbergh, Annika, et al.
(författare)
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Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:2, s. 557-562
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.
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| 22. |
- Wennerberg, Johan, et al.
(författare)
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Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity : The ARTSCAN 2 study
- 2022
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 166, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeAn earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.Materials and methodsPatients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.Results250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.Toxicity was more pronounced in preoperative AF.ConclusionThis study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.
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