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1.
  • Malmström, Annika, 1957- (författare)
  • Studies for Better Treatment of Patients with Glioma
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.
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2.
  • Gerdtsson, Axel, et al. (författare)
  • Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group
  • 2022
  • Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:2, s. 235-243
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
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3.
  • Asplund, Dan, et al. (författare)
  • Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence
  • 2017
  • Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 32:11, s. 1639-1647
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Quality of life may predict survival. In addition to clinical variables, it may be influenced by psychological factors, some of which may be accessible for intervention. The primary objective of this study was to investigate the association of intrusive thoughts and the patients' sense of coherence with pretreatment quality of life in patients with newly diagnosed rectal cancer. Methods Patients were prospectively included in 16 hospitals in Sweden and Denmark. They answered an extensive questionnaire after receiving their treatment plan. Clinical data were retrieved from national quality registries for rectal cancer. Results Of 1248 included patients, a total of 1085 were evaluable. Pretreatment global health-related and overall quality of life was lower in patients planned for palliative compared with curative treatment (median 53 vs. 80 on the EuroQoL visual analogue scale, p < 0.001 and odds ratio 0.56, 95% confidence interval 0.36-0.88, respectively). Quality of life was associated with intrusive thoughts (odds ratio 0.33, 95% confidence interval 0.24-0.45) and sense of coherence (odds ratio 0.44, 95% confidence interval 0.370.52) irrespective of the treatment plan. Conclusions Pretreatment quality of life was influenced by the intent of treatment as well as by intrusive thoughts and the patients' sense of coherence. Interventions could modify these psychological factors, and future studies should focus on initiatives to improve quality of life for this group of patients.
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4.
  • Landberg, Rikard, et al. (författare)
  • Reproducibility of plasma alkylresorcinols during a 6-week rye intervention study in men with prostate cancer
  • 2009
  • Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 139:5, s. 975-980
  • Tidskriftsartikel (refereegranskat)abstract
    • Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as concentration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% CI = 0.82-0.98], intervention period 2: ICC = 0.88 [95% CI = 0.78-0.98]). The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of +/- 20% (80% CI). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant.
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5.
  • Gerdtsson, Axel, et al. (författare)
  • Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour : A Population-based Study from the Swedish Norwegian Testicular Cancer Group
  • 2020
  • Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 3:3, s. 382-389
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.
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6.
  • Ostman, Maria, et al. (författare)
  • Novel Calcium Phosphate Promotes Interbody Bony Fusion in a Porcine Anterior Cervical Discectomy and Fusion Model
  • 2024
  • Ingår i: Spine. - : Wolters Kluwer. - 0362-2436 .- 1528-1159. ; 49:17, s. 1179-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design: Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study.Objective.The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and beta-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model.Summary of Background Data: ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases. However, pseudarthrosis associated with increased patient morbidity occurs in similar to 2.6% of the surgeries. SBG may enhance bony fusion and subsequently decrease the risk of pseudarthrosis. Recent studies on monetite-based SBGs for use in large cranial defects in humans have shown promising bone healing results, necessitating further investigation of their use in cervical spinal fusion.Materials and Methods: Four adult female Danish G & ouml;ttingen minipigs received partial cervical anterior discectomy and intervertebral defects at an upper and lower level. One defect was filled with SBG, and the other was left empty. Bony fusion was evaluated using computed tomography (CT) at three-month intervals for 12 months. Fifteen months postsurgery, the animals were euthanized for further ex vivo qualitative histopathologic and micro-CT evaluations. Fusion rates were compared using the Fisher exact test at each time point.Results.Increased interbody bony fusion rates were observed at SBG levels (4/4) compared with control levels (0/4) evaluated by CT at 6 and 9 months postsurgery (P=0.029). Fusion was observed at all SBG levels 12 months postsurgery and at only one control level. Histopathologic evaluation confirmed high-quality interbody bony fusion at all SBG levels and fusion by spondylosis at one control level.Conclusion: This proof-of-concept study provides preliminary evidence of a novel, calcium pyrophosphate-containing, and beta-tricalcium phosphate-containing monetite SBG that promotes bony fusion compared with a negative control in a clinically relevant porcine model of ACDF.
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7.
  • Hansen, Louise, et al. (författare)
  • Intake of dietary fiber, especially from cereal foods, is associated with lower incidence of colon cancer in the HELGA cohort
  • 2012
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 131:2, s. 469-478
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of dietary fiber on the risk of colon and rectal cancer has been investigated in numerous studies, but findings have been inconsistent. The purpose of this study was to examine associations between intake of dietary fiber and risk of incident colon (including distal and proximal colon) and rectal cancer in the prospective Scandinavian HELGA cohort and to determine if fiber source (vegetables, fruits, potatoes, cereals) impacted the association. We included 1,168 incident cases (691 colon, 477 rectal cancer), diagnosed during a median of 11.3 years, among 108,081 cohort members. Sex-specific incidence rate ratios (IRRs) of colon and rectal cancer were related to intake of total or specific fiber source using Cox proportional hazards models. For men, an inverse association was observed between intake of total fiber and the risk of colon cancer per an incremental increase of 10 g day(-1) , IRR (95% CI): 0.74 (0.64-0.86). Intake of cereal fiber per 2 g day(-1) was associated with an IRR of 0.94 (0.91-0.98), which was also seen for intake of cereal fiber from foods with high fiber content (≥5 g per 100 g product), where the IRR per 2 g day(-1) was 0.94 (0.90-0.98). In women, intake of cereal fiber per 2 g day(-1) was also associated with lower risk of colon cancer, 0.97 (0.93-1.00). No clear associations were seen for rectal cancer. Our data indicate a protective role of total and cereal fiber intake, particularly from cereal foods with high fiber content, in the prevention of colon cancer.
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8.
  • Stattin, Pär, et al. (författare)
  • Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study
  • 2017
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:1, s. 125-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance. Objective: To investigate the association between radical local treatment and mortality in men with very high-risk PCa. Design, setting, and participants: Semiecologic study of men aged < 80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998-2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50-200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level < 50 ng/ml, any N, and M0) were used as positive controls. Intervention: Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis. Outcome measurements and statistical analysis: PCa and all-cause mortality rate ratios (MRRs). Results and limitations: Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28-0.95; and all-cause MRR: 0.56; 95% CI, 0.33-0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposurewere in agreement with results fromrandomized trials (PCaMRR: 0.75; 95% CI, 0.60-0.94; and all-cause MRR: 0.85; 95% CI, 0.72-1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity. Conclusions: The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective. Patient summary: Menwith very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality. (C) 2016 European Association of Urology. Published by Elsevier B.V.
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9.
  • Olsson, Marie, et al. (författare)
  • Effects of extracts of apple peel from organically and integrated production cultivated apples and ursolic acid on cancer cell proliferation
  • 2014
  • Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. - 9789462610286 ; 1040, s. 227-230
  • Konferensbidrag (refereegranskat)abstract
    • The effects of extract of apple peel, 'Aroma', organically cultivated or cultivated according to integrated production, on cell proliferation in vitro of colon cancer HT29 cells and breast cancer MCF-7 cells, were investigated. Different sequences of solvents were used, and the inhibiting effect on cancer cell proliferation of the different extracts was investigated. The solvents used were ethanol, methanol, DMSO and hexane in different sequences. The extracts decreased the proliferation of both HT29 and MCF-7 cells, the effect was different for the different extracts, and ethanol showed the highest inhibition effect. The inhibiting effect of the extracts also varied between both apple production methods, and extracts from peels of organically produced apples showed in some cases higher inhibition effects, while sometimes no differences were found. In addition, as ursolic acid, a component of apple peel, has been proposed to inhibit cancer cell proliferation, the inhibiting effect of pure ursolic acid on cancer cell proliferation was compared with the effect of the apple peel solvent fraction with the highest ursolic acid concentration. The inhibiting effect was higher in the apple fraction extract than in pure ursolic acid. Further, a range of different apple cultivars, integrated production and organically cultivated, were analysed by HPLC for their content of ursolic acid to investigate possible differences in concentrations.
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10.
  • Hilborn, Erik, 1988- (författare)
  • The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer : Impact on tamoxifen treatment
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast  cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different  aspects of their role in breast cancer.Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.
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