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Practical Radiation Oncology Jun 2024SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and...
PURPOSE
SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer.
METHODS AND MATERIALS
Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed.
RESULTS
From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity.
CONCLUSIONS
The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer.
PubMed: 38944806
DOI: 10.1016/j.prro.2024.04.022 -
Biochemical Pharmacology Jun 2024Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA...
Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA is a fat-soluble active ingredient obtained from Salvia miltiorrhiza, which has an inhibitory effect against various cancers. We designed and synthesized a novel L-shaped ortho-quinone analog TE5 with tanshinone IIA as the lead compound and tested its antitumor activity against GBM. The results indicated that TE5 effectively inhibited the proliferation, migration, and invasion of GBM cells, and demonstrated low toxicity in vitro. We found that TE5 may bind to androgen receptors and promote their degradation through the proteasome. Inhibition of the PI3K/AKT signaling pathway was also observed in TE5 treated GBM cells. Additionally, TE5 arrested the cell cycle at the G2/M phase and induced mitochondria-dependent apoptosis. In vivo experiments further confirmed the anti-tumor activity, safety, and effect on androgen receptor level of TE5 in animal models of GBM. Our results suggest that TE5 may be a potential therapeutic drug to treat GBM.
PubMed: 38944395
DOI: 10.1016/j.bcp.2024.116398 -
Food and Chemical Toxicology : An... Jun 2024Nanosilver (AgNPs) is popular nanomaterials used in food industry that makes gastrointestinal tract an essential route of its uptake. The aim of the presented study was...
Nanosilver (AgNPs) is popular nanomaterials used in food industry that makes gastrointestinal tract an essential route of its uptake. The aim of the presented study was to assess the effects of intragastric exposure to AgNPs on redox balance and steroid receptors in the testes of adult Fisher 344 rats. The animals were exposed to 20 nm AgNPs (30 mg/kg bw/day, by gavage) for 7 and 28 days compared to saline (control groups). It was demonstrated that 7-day AgNPs administration resulted in increased level of total antioxidant status (TAS), glutathione reductase (GR) activity, lower superoxide dismutase activity (SOD), decreased glutathione (GSH) level and GSH/GSSG ratio, as well as higher estrogen receptor (ESR2) and aromatase (Aro) protein expression in Leydig cells compared to the 28-day AgNPs esposure. The longer-time effects of AgNPs exposition were associated with increased lipid hydroperoxidation (LOOHs) and decreased SOD activity and androgen receptor protein level. In conclusion, the present study demonstrated the adverse gastrointestinally-mediated AgNPs effects in male gonads. In particular, the short-term AgNPs exposure impaired antioxidant defence with concurrent effects on the stimulation of estrogen signaling, while the sub-chronic AgNPs exposition revealed the increased testicle oxidative stress that attenuated androgens signaling.
PubMed: 38944145
DOI: 10.1016/j.fct.2024.114841 -
Psychoneuroendocrinology Jun 2024Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still...
Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether these effects are modulated by stress. The study comprised 130 female participants, half of whom were using oral contraceptives, while the other half were not using any hormonal contraception (NC). The participants completed the Approach Avoidance Task (AAT), which measures automatic approach and avoidance behavior to socio-affective signals. The AAT was run once before and once after a stress manipulation using the Socially Evaluated Cold Pressor Test. OC users showed absent avoidance behavior to social threat signals and a stress-induced increase in approach behavior to positive social signals. The latter was found in particular in women taking androgenic acting OC, demonstrating that different OC preparations need to be taken into account in research on OC effects. However, OC and NC group did not differ in their cortisol stress response. Overall, the results suggest that OC usage impacts on approach and avoidance behavior to social signals, which might also contribute to the development of affective side effects.
PubMed: 38943719
DOI: 10.1016/j.psyneuen.2024.107111 -
Cancer Jul 2024
Topics: Humans; Prostatic Neoplasms; Male; Androgen Antagonists; Antineoplastic Agents, Hormonal
PubMed: 38943470
DOI: 10.1002/cncr.35422 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Atrazine (ATZ, CHClN) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways...
Atrazine (ATZ, CHClN) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways involved in hormone signaling, and DNA damage, and can cause reproductive disorders, including decreased fertility, and abnormal development of reproductive organs, as revealed in animal model studies. However, the effect of ATZ on steroidogenesis in the male reproductive system, especially reduction of ketosteroids to hydroxysteroids, remains unclear. This study investigated the toxicity of ATZ on the male reproductive system in the Wistar rat model, with an emphasis on its adverse effect on aldo-ketoreductase family 1 member C2 (AKR1C2). Male Wistar rats were administered ATZ for 56 days (duration of one spermatogenic cycle) through oral route, at 20, 40 and 60 mg/kg body weight (bw) doses. The results indicate that ATZ exposure affects the body weight, impairs sperm production, and decrease FSH, LH, and testosterone levels. Additionally, the down-regulation of key steroidogenic enzymes by ATZ disrupted the synthesis of testosterone, leading to decreased levels of this essential male hormone. On the other hand, the expression of AKR1C2 (mRNA and protein) in the testis was upregulated. The findings suggest that AKR1C2 plays a role in androgen metabolism. Furthermore, its overexpression may lead to alteration in the expression of genes in the connected pathway, causing an increase in the breakdown or inactivation of androgens, which would result in lower androgen levels and, thereby, lead to hypoandrogenism, as the combined effects of down-regulation of steroidogenic genes and up-regulation of AKR1C2. These findings reveal direct implication of disrupted AKR1C2 in male reproductive health and highlight the need for further research on the impact of environmental toxins on human fertility, ultimately providing for better patient care.
PubMed: 38943029
DOI: 10.1007/s43032-024-01627-3 -
European Journal of Nuclear Medicine... Jun 2024Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal...
Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.
PURPOSE
Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.
METHODS
A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.
RESULTS
Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.
CONCLUSIONS
Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.
PubMed: 38940843
DOI: 10.1007/s00259-024-06802-x -
Science China. Life Sciences Jun 2024
PubMed: 38940831
DOI: 10.1007/s11427-024-2652-y -
Clinical Cancer Research : An Official... Jun 2024To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PURPOSE
To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PATIENTS AND METHODS
This was an open-label, single-arm, multicenter phase II study for patients with AR-positive URM-SGC. The primary endpoint was the overall response rate (ORR) by an independent central radiology review (ICRR) in the first 24 response evaluable patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded.
RESULTS
31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by ICRR was 25.0% (6/24 patients; 95%CI: 9.8%-46.7%; P =0.11 (one-sided)), which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR-positivity ≥ 70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain.
CONCLUSIONS
Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive SGC and safety consistent with prior experience in prostate cancer.
PubMed: 38940667
DOI: 10.1158/1078-0432.CCR-24-0455 -
The European Journal of Contraception &... Jun 2024To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users.
PURPOSE
To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users.
MATERIALS AND METHODS
Six months modification in the McCoy Female Sexuality Questionnaire (MFSQ) and testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) serum levels in women starting a monophasic pill containing ethinyl-estradiol (EE) 35 µg and NGM 0.250 mg.
RESULTS
The study was completed by 36 subjects. There was a significant increase in MFSQ during treatment ( < 0.0001) (and its domains with the exclusion of vaginal lubrication domain) with concomitant decreases in T (-4.45%, < 0.0001) and DHEAS (-19.41%, < 0.0001) serum levels.
CONCLUSIONS
Contraception with EE/NGM was associated with a short term non-deteriorating effect on sexuality despite the evident decrease in androgen levels. Female sexuality during COC use is a complex topic and is not only linked with changes in serum androgen levels.
PubMed: 38940613
DOI: 10.1080/13625187.2024.2369833