Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración?

ObjectiveProstate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies.Material and methodsThis clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients’ progression time after Dx therapy and the effects on sequential treatment.ResultsAfter Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (P<.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months.ConclusionsOur findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.     

Control of immunity and allergy by steroid hormones

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice.     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.     

前列腺癌去势术前后雄性激素变化的研究

目的 :观察前列腺癌去势术前后雄性激素的变化。　方法 :16例前列腺癌病人在手术前后分别采集血清样本 ,用放射免疫法测定睾酮 (T)、游离睾酮 (FT)、双氢睾酮 (DHT)的含量 ,进行对比分析。　结果 :手术前后 ,血清中T、FT、DHT浓度有非常明显的差异 ,手术后分别下降 92 .2 7%、92 .2 6%、5 8.3 6% ,以T、FT下降为主。根据 2次测定的结果采用配对t检验方法 ,P <0 .0 0 1。　结论 :去势术后 ,去除了血清中绝大部分T、FT ,而DHT仅下降5 8.3 6% ,应当继续使用雄性激素受体竞争剂 ,阻止残存的雄性激素作用     

Intrauterine position affects motoneuron number and muscle size in a sexually dimorphic neuromuscular system

The intrauterine position occupied by a rodent fetus influences the amount of testosterone to which it is exposed before birth. Animals that are gestated between two male fetuses (2M) are exposed to higher circulating levels of testosterone than are animals positioned between two female fetuses (2F) and there are reliable differences in the reproductive physiology and behavior of 2M and 2F animals when adult. To determine whether intrauterine position modifies development of the central nervous system, we examined the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) in male and female gerbils from known intrauterine positions. We found that adult 2M female gerbils had 16% more SNB motoneurons than did 2F females. 2M males did not differ from 2F males in SNB motoneuron number, but the bulbocavernosus muscle, which is innervated by SNB motoneurons, was approximately 50% larger in 2M than in 2F males. These data indicate that intrauterine position can influence the morphology of the sexually dimorphic SNB neuromuscular system.     

男性激素避孕临床研究的某些进展

随着社会的发展 ,迫切需要研制可供男性选用、安全高效、可复性和可接受性均好的避孕药。男性激素类避孕是当今最有前途的方法之一 ,其基本原理是通过外源性激素来抑制垂体促性腺激素和睾丸内睾酮的合成与分泌 ,进而抑制精子发生 ;同时给予的外源雄激素维持男性性征和性功能。研究中的男性激素避孕方法 ,包括单用雄激素、雄激素与孕激素合用、GnRH类似物与雄激素合用、激素相关的免疫途径等 ,寻求更长效、使用更方便、副作用小的雄激素制剂也是当今研究的重点之一     

Cellular localization of immunoreactive epidermal growth factor during Wolffian duct differentiation of the fetal mouse

Previous studies from this laboratory indicated a role for epidermal growth factor (EGF) in androgen-dependent male reproductive tract differentiation of the fetal mouse. Expression of an EGF-like protein during Wolffian duct differentiation was indicated from the determinations by radioimmunoassay (RIA) and radioreceptor assay. To further characterize the protein and to assess its role in male sexual differentiation, expression of the protein has been analyzed by Western blot assay and its tissue-specific cellular expression has been determined by immunocytochemical assay in the present study. Western blot analysis of the 18-day fetal male reproductive tract detected an immunoreactive band of the predicted 6-kDa size. Immunocytochemical analysis also detected EGF-specific immunostaining in the Wolffian duct derivatives. At day 18 of gestation, the staining was localized predominantly in the epithelial nuclei of the Wolffian duct derivatives whereas at days 14 and 16 of gestation, the staining was equally distributed in the mesenchymal and epithelial sites of the Wolffian duct derivative. The intensity of the staining increased with progression of differentiation during the 14th–18th days of gestation. Prenatal exposure to the antiandrogen flutamide significantly reduced the immunostaining of the duct. Thus, a role for EGF in Wolffian duct differentiation is indicated.