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Marike Gabrielson Mattias Hammarström Magnus Bäcklund Jenny Bergqvist Kristina Lång Ann H Rosendahl Signe Borgquist Roxanna Hellgren Kamila Czene Per Hall 《International journal of cancer. Journal international du cancer》2023,152(11):2362-2372
Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen. 相似文献
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Signe S?nderkaer Marianne Schmiegelow Henrik Carstensen Lars B?geskov Nielsen J?rn Müller Kjeld Schmiegelow 《Journal of clinical oncology》2003,21(7):1347-1351
PURPOSE: To evaluate the pattern of neurological late effects in patients who have received surgery only for a brain tumor in childhood and to identify possible risk factors for neurological sequelae. PATIENTS AND METHODS: The medical, histologic, and operative records were reviewed for 65 consecutive patients operated for a benign brain tumor from 1970 to 1997, and all patients were re-examined after a median length of follow-up of 10.7 years. Thirty-four patients had posterior fossa tumors, 22 patients had cerebral hemisphere tumors, and nine patients had midline tumors. RESULTS: At the time of follow-up, 20 patients (31%) had no neurological deficits, 22 patients (34%) had minor deficits that did not interfere with their daily life activities, and 23 patients (35%) had moderate or severe deficits such as severe ataxia, spastic paresis, seriously reduced vision, or epilepsy with more than two seizures per year. Fourteen of the 31 patients (45%) registered with ataxia preoperatively had recovered fully. Six of seven patients had persistence of a pre- or postoperatively developed hemiparesis. Thirteen of 23 patients had persistence of cranial nerve deficits that developed second to surgery. Fifty-five percent of the 18 patients with seizures at diagnosis were seizure-free at follow-up. At follow-up both ataxia and hemiparesis were significantly more frequent among females (P =.02 and P =.03, respectively). CONCLUSION: In patients who received operation as the only treatment for their brain tumor, there was a good chance of total or partial recovery of preoperative and postoperative neurological deficits, although only one third of the patients will have no long-term neurological deficits. 相似文献
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Smad4 overexpression causes germ cell ablation and leydig cell hyperplasia in transgenic mice
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Narula A Kilen S Ma E Kroeger J Goldberg E Woodruff TK 《The American journal of pathology》2002,161(5):1723-1734
Members of the transforming growth factor-beta (TGF-beta) superfamily play a variety of important roles in testicular development and function. The tumor suppressor gene, Smad4, is a common mediator of TGF-beta, activin, and bone morphogenetic protein-mediated signaling pathways. To investigate the role of the Smad4 gene during testicular development and function, transgenic mice were generated using a Flag-tagged Smad4 gene driven by 180-bp fragment of the Mullerian inhibiting substance upstream promoter sequence. Three Smad4 transgenic founders (A, B, and G) were detected by Southern blot analysis; line B showed the highest expression of the Smad4 transgene and was further studied. The fertility in F1 generation (B) and F2 generation (BB) of the Smad4 transgenic mice was not impaired. However, in the F3 generation (B2x) all animals were impacted by the overexpression of the Smad4 transgene and two kinds of phenotypes were observed. In one group animals were completely infertile, while in the other group animals were fertile and sired the normal number of pups/litter. These groups are designated as infertile and fertile in the text. Histological evaluation of the testes from the infertile group showed variable degrees of Leydig cell hyperplasia, apoptosis of germ cells, spermatogenic arrest, seminiferous tubule degeneration, and infertility. In the fertile group, there was no apparent change in the histology of the testis except for a slight increase in the number of Leydig cells. Serum follicle-stimulating hormone levels in the adult animals of both groups of Smad4 transgenic male mice were not significantly different from normal littermates; however, testosterone levels in both groups were significantly (P < 0.05) increased. These results suggest that overexpression of Smad4 leads to testicular abnormalities and infertility supporting the hypothesis that the TGF-beta signaling pathways are carefully orchestrated during testicular development. In the absence of normal levels of Smad4 testicular function is compromised. 相似文献
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Wim P.J. Witjes Michel J. A.M. De Wildt Peter F.W.M. Rosier Christine T.M. Caris Frans M.J. Debruyne Jean J.M.C.H. De La Rosette 《The Journal of urology》1996,156(3):1026-1034
Purpose
We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement.Materials and Methods
Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period of watchful waiting.Results
Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decrease in detrusor pressure at maximal flow of 14 cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction.Conclusions
Mean differences among therapy groups must be regarded critically, especially when the differences are slight and possibly within physiological variability. 相似文献9.
K. Ezz El Din W.F.R.M. Koch M.J. A.M. de Wildt L.A.L.M. Kiemeney F.M.J. Debruyne J.J.M.C.H. de la Rosette 《The Journal of urology》1996,155(6):1959-1964
Purpose
The reliability of the International Prostate Symptom Score (I-PSS) was tested in patients with lower urinary tract symptoms and/or benign prostatic hyperplasia.Materials and Methods
A total of 71 consecutive men with benign prostatic hyperplasia and/or lower urinary tract symptoms was asked to complete the I-PSS at baseline and 8 weeks later. At the second visit the physician also completed the I-PSS according to the complaints of the patient. Variability between both scores was evaluated by calculation of duplo errors and results were compared to the clinical data.Results
A considerable variability existed between the I-PSS results obtained at baseline and 8 weeks. The duplo error was 4.3. In a regression analysis of I-PSS, including all clinical parameters, only free flow had some predictive value for I-PSS outcomes.Conclusions
It is important to consider the variability of the I-PSS score when making decisions concerning treatment. 相似文献10.
Wim P.J. Witjes Peter F.W.M. Rosier Michel J. A.M. de Wildt Matheus P. van Iersel Frans M.J. Debruyne Jean J.M.C.H. de la Rosette 《The Journal of urology》1996,155(4):1317-1323