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Revista Da Associacao Medica Brasileira... Sep 2019Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among...
Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among other things, cyclic AMP. Notwithstanding all the literature data, there is still no sound knowledge or a clear understanding of the hormone's action on the physiology of ovarian follicular cells. OBJECTIVE To review and evaluate studies about melatonin action on the ovarian granulosa/theca interna cells from the literature. METHODS The systematic review was carried out according to the PRISMA recommendations. The MEDLINE and Cochrane primary databases were consulted with the use of specific terms. There was no limitation on language or publication year. RESULTS Seven papers about melatonin action on granulosa cells were selected. The following can be attributed to the hormone's effects: a) progesterone increase in culture medium; b) increased estrogen production; c) antagonistic action on estrogen; d) improvement in cell quality resulting in improved embryo and higher pregnancy rates; e) improved cell proliferation via MAPK; f) reduction of free radicals. Nevertheless, there are contrarian papers reporting a reduction in progesterone production. Melatonin interferes in sex steroid production, boosting progesterone output. Such action may help improve oocyte quality.
Topics: Cells, Cultured; Female; Granulosa Cells; Humans; Melatonin; Oocytes; Ovarian Follicle; Pregnancy; Progesterone; Theca Cells
PubMed: 31531613
DOI: 10.1590/1806-9282.65.8.1122 -
Neurology India 2019Surgery is challenging in patients with multiple or recurrent meningiomas. With the discovery of progesterone receptors (PR) on meningioma cells, there is an increased...
BACKGROUND
Surgery is challenging in patients with multiple or recurrent meningiomas. With the discovery of progesterone receptors (PR) on meningioma cells, there is an increased interest in the hormonal treatment using mifepristone, a PR blocker.
MATERIALS AND METHODS
A systematic review of clinical studies evaluating the efficacy and side effects of mifepristone in recurrent, unresectable, or multiple meningiomas was done. The primary outcome of this review was to study the efficacy in terms of tumor regression and clinical symptoms. Secondarily, we also reviewed the frequency and severity of different side effects reported by various studies.
RESULTS
A total of 7 studies, including one Phase III randomized controlled trial, were found relevant to the topic. Though a few studies showed some response in terms of clinical improvement and tumor size reduction, the response was either minimal or temporary. The only subset showing a good response was the "diffuse meningiomatosis" group. None of the studies evaluated the relation of the PR isoform with mifepristone responsiveness. However, long-term mifepristone administration was well tolerated in most of the patients.
CONCLUSIONS
Use of mifepristone as a hormonal agent for meningiomas has produced mixed results. We propose that the possible mechanisms of action of mifepristone on meningioma cells must be studied in further detail by in-vitro studies. This may help in the identification of a mifepristone responsive subset of meningioma. This must be followed up with appropriately designed clinical studies with detailed baseline evaluation and standardized clinical and radiological follow-up.
Topics: Humans; Meningeal Neoplasms; Meningioma; Mifepristone; Neoplasm Recurrence, Local; Receptors, Progesterone; Treatment Outcome
PubMed: 31347538
DOI: 10.4103/0028-3886.263232 -
Journal of Experimental & Clinical... May 2019Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor...
Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.
Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Movement; Cell Proliferation; Drug Resistance, Neoplasm; Humans; Molecular Targeted Therapy; Neoplastic Stem Cells; Neovascularization, Pathologic; Oncogenes; STAT3 Transcription Factor; Signal Transduction; Triple Negative Breast Neoplasms; Tumor Escape
PubMed: 31088482
DOI: 10.1186/s13046-019-1206-z -
Targeted Oncology Apr 2019Several endocrine therapies are available for postmenopausal women with hormone receptor-positive (HR +) advanced breast cancer (ABC). Given the absence of direct... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Efficacy of CDK4/6 Inhibitors Plus Aromatase Inhibitors Versus Fulvestrant for the First-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer: A Network Meta-Analysis.
BACKGROUND
Several endocrine therapies are available for postmenopausal women with hormone receptor-positive (HR +) advanced breast cancer (ABC). Given the absence of direct comparisons between fulvestrant and cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with aromatase inhibitors (AIs), which are both used as standard first-line treatments for ABC, an indirect comparison using a network meta-analysis may be advantageous for decision making.
OBJECTIVE
We performed a network meta-analysis to compare the efficacies of fulvestrant and CDK4/6is plus AIs as the first-line treatment of postmenopausal breast cancer patients.
PATIENTS AND METHODS
In order to compare these treatments, we searched the PubMed, Cochrane Library, and EMBASE databases for randomized controlled trials of first-line endocrine treatment for advanced or metastatic breast cancer until October 2018. We included a total of 11 eligible trials with 5448 patients. The hazard ratios (HRs) for the efficacies of the different treatments were used as inputs in the network meta-analysis.
RESULTS
In the overall analysis, CDK4/6is plus AIs, including palbociclib plus letrozole, ribociclib plus letrozole, and abemaciclib plus nonsteroidal AI (letrozole or anastrozole), are all superior to 500 mg fulvestrant (HR = 0.50, 95% confidence interval [CI] 0.37-0.68; HR = 0.50, 95% CI 0.35-0.71; and HR = 0.49, 95% CI 0.34-0.71; respectively).
CONCLUSIONS
Within the limitations of this network meta-analysis, the comparison indicates that CDK4/6is plus AIs might represent a better option for HR+ ABC as a first-line endocrine treatment compared with fulvestrant.
Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials as Topic; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Fulvestrant; Humans; Letrozole; Network Meta-Analysis; Piperazines; Purines; Pyridines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 30941621
DOI: 10.1007/s11523-019-00633-9 -
Acta Obstetricia Et Gynecologica... Feb 2019The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent... (Review)
Review
INTRODUCTION
The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent spontaneous preterm birth in women with a prophylactic cerclage.
MATERIAL AND METHODS
Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before June 2018. Keywords included "preterm birth", "prophylactic cerclage", "history-indicated cerclage", "pregnancy" and "17-hydroxyprogesterone caproate". Studies comparing history-indicated cerclage alone with cerclage+17-OHPC were included. The primary outcome measure was preterm birth at <24 weeks of gestation. Secondary outcome measures include preterm birth at <28 weeks, <32 weeks and <37 weeks of gestation, respiratory distress syndrome, necrotizing enterocolitis, fetal birthweight, neonatal intensive care unit stay, mean gestational age at delivery, fetal/neonatal death, neurological morbidity (intraventricular hemorrhage plus periventricular leukomalacia), neonatal sepsis and a composite of severe neonatal morbidity. Severe neonatal morbidity was defined as a composite measure of periventricular leukomalacia, intraventricular hemorrhage (grades III and IV), necrotizing enterocolitis or respiratory distress syndrome. Meta-analysis was performed using the random-effects model of DerSimonian and Laird. Risk of bias and quality assessment were performed using the ROBINS-I and GRADE tools, respectively. PROSPERO Registration Number: CRD42018094559.
RESULTS
Five studies met the inclusion criteria and were included in the final analysis. Of the 546 women, 357 (75%) received history-indicated cerclage alone and 189 (35%) received adjuvant 17-OHPC. The composite endpoint, severe neonatal morbidity, was present in 84 of 1515 neonates. Though there was a trend toward a reduced risk of preterm birth, the summary estimate of effect was not statistically significant when comparing cerclage alone with cerclage+17-OHPC at <24 weeks (relative risk [RR] .86, 95% confidence interval [CI] .45-1.65). Similarly, we found no differences in preterm birth at <37 weeks (RR .90, 95% CI .70-1.17) and <28 weeks (RR .85, 95% CI .54-1.32) when comparing cerclage alone with cerclage+17-OHPC. There were no differences in fetal birthweight, respiratory distress syndrome or necrotizing enterocolitis comparing cerclage alone with cerclage+17-OHPC.
CONCLUSIONS
Intramuscular 17-OHPC in combination with prophylactic cerclage in women with prior preterm birth had no synergistic effect in reducing spontaneous recurrent preterm birth or improving perinatal outcomes.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Cerclage, Cervical; Combined Modality Therapy; Estrogen Antagonists; Female; Humans; Pregnancy; Premature Birth; Secondary Prevention
PubMed: 30339274
DOI: 10.1111/aogs.13488 -
Breast Cancer Research and Treatment Nov 2018Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a meta-analysis of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a meta-analysis of randomized clinical trials (RCTs) to better define the benefit and the risk of CDK4/6 inhibitors plus ET for endocrine-sensitive or endocrine-resistant population in metastatic HR+/HER2- breast cancer.
METHOD
A systematic literature search of Pubmed, Embase, and the Cochrane Library was carried out up to 30 June 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS), as well as odds ratios (ORs) for objective response rates, ≥ G3-G4 adverse events (AEs), and G3-G4 neutropenia were calculated for each trial. A meta-analysis was carried out using the random-effects model.
RESULTS
Eight RCTs were eligible including 4578 breast cancer patients. Adding CDK4/6 inhibitors to ET in endocrine-sensitive (HR 0.55, 95% CI 0.50-0.62) or endocrine-resistant setting (HR 0.51, 95% CI 0.43-0.61) significantly improved the PFS of metastatic HR+/HER2- breast cancers regardless of menopausal status and site of metastasis. Moreover, CDK4/6 inhibitors plus ET meaningfully improved objective response rate in endocrine-sensitive (ORs 0.62, 95% CI 0.52-0.73) or endocrine-resistant setting (ORs 0.33, 95% CI 0.24-0.47). The use of these drugs was characterized by a significant increase of G3-G4 AEs (OR 10.88, 95% CI 6.53-18.14).
CONCLUSION
Emerging data provide a new standard treatment for advanced HR+/HER2- breast cancer, regardless of menopausal status, prior hormonal/chemotherapy treatments delivered, sites of metastasis. However, benefits should be balanced with longer treatment duration, toxicities, and costs.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Neoplasm Metastasis; Progression-Free Survival; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 30054831
DOI: 10.1007/s10549-018-4901-0 -
Clinical Breast Cancer Oct 2018This meta-analysis of randomized controlled trials aimed to comprehensively assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in advanced... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
This meta-analysis of randomized controlled trials aimed to comprehensively assess the efficacy and toxicity of cyclin-dependent kinase (CDK) 4/6 inhibitors in advanced breast cancer (ABC) with hormone-receptor positive (HR) and human epidermal growth factor receptor 2 negative (HER2) disease.
METHODS
We performed a systematical search using Cochrane Library, PubMed, Embase, and Web of Science up to March 2018. Only phase 2 and 3 randomized clinical trials assessing the efficacy and toxicity of the combination regimen of CDK4/6 inhibitors plus hormone therapy compared with hormone therapy alone were eligible for this meta-analysis. The pooled analyses of relative risk (RR) and hazard ratio were carried out by Stata software.
RESULTS
A total of 7 randomized controlled trials including 3854 patients with HR/HER2 ABC were included in this meta-analysis. The pooled hazard ratio for progression-free survival was 0.54 (95% confidence interval, 0.49-0.59; P < .001), and the pooled RR for the objective response rate in all intent-to-treat patients was 1.51 (95% confidence interval, 1.26-1.81; P < .001). The pooled RRs for all grade adverse events (AEs) and grade 3/4 AEs were 1.07 (95% confidence interval, 1.03-1.11; P < .001) and 2.81 (95% confidence interval, 2.54-3.11; P < .001), respectively. However, to investigate the influence of CDK4/6 inhibitors on overall survival, sufficient follow-up is still needed.
CONCLUSION
CDK4/6 inhibitors plus hormone therapy can significantly prolong the progression-free survival of patients with HR/HER2 ABC and improve the objective response rate compared to conventional hormone therapy alone. The combined regimen results in a higher risk of AEs, especially grade 3/4 AEs.
Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Middle Aged; Odds Ratio; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome
PubMed: 29804650
DOI: 10.1016/j.clbc.2018.04.017 -
Genetic Testing and Molecular Biomarkers May 2018Steroid hormones play a central role in modulating the growth of uterine leiomyoma, and several studies have suggested that polymorphisms in genes encoding these... (Meta-Analysis)
Meta-Analysis Review
AIMS
Steroid hormones play a central role in modulating the growth of uterine leiomyoma, and several studies have suggested that polymorphisms in genes encoding these hormones and their receptors may be risk factors for developing the disease. Progesterone is a potent antagonist of estrogen-induced proliferation in the endometrium, and the PROGINS polymorphisms have been associated with leiomyoma, but the results are inconsistent. In this study, we aimed to investigate the possible associations between the PROGINS polymorphisms and uterine leiomyoma.
MATERIALS AND METHODS
MEDLINE using PubMed, Science Direct, and Google Scholar databases was searched using the terms "PROGINS," "progesterone receptor," "polymorphism," and "leiomyoma." We estimated risk with odds ratios [ORs] and 95% confidence intervals using standard genetic models (homozygous, recessive, dominant, and codominant).
RESULTS
Six studies were included in this meta-analysis based on 837 cases and 1011 controls. Subjects in three studies were Asian (365 cases/391 controls), and five were non-Asian (472 cases/620 controls). Our findings showed no association between PROGINS and leiomyoma in the overall analysis (OR 0.91-1.07, p = 0.15-0.57) nor in either of the subgroups (Asian: OR 0.84-1.04, p = 0.68-0.98; or non-Asian: OR 0.77-1.34, p = 0.33-0.93), in all genetic models.
CONCLUSION
The PROGINS polymorphisms cannot be considered a risk factor for developing uterine leiomyoma.
Topics: Female; Humans; Leiomyoma; Polymorphism, Genetic; Receptors, Progesterone; Risk Factors; Uterine Neoplasms
PubMed: 29630404
DOI: 10.1089/gtmb.2017.0233 -
The Turkish Journal of Gastroenterology... Dec 2017Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use... (Review)
Review
Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.
Topics: Drug-Related Side Effects and Adverse Reactions; Esophagus; Gastroesophageal Reflux; Humans; Risk Factors
PubMed: 29199166
DOI: 10.5152/tjg.2017.11 -
Clinical Chemistry and Laboratory... Apr 2018Epidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR-inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are involved in...
Epidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR-inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments. The aim is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review was conducted in accordance to the PRISMA guidelines. Literature searches were conducted to identify publications exploring correlations between EGFR/EGFR-ligands in serum/plasma of breast cancer patients and prognostic/predictive outcome measures. Sixteen publications were eligible for inclusion. Twelve studies evaluated EGFR, whereas five studies evaluated one or more of the EGFR-ligands. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced breast cancer, especially in patients with estrogen and/or progesterone receptor positive tumors. The prognostic and predictive value of EGFR and EGFR-ligands in blood has only been investigated in highly selected subsets of breast cancer patients and most studies were small. This is the first systematic review evaluating the utility of EGFR and EGFR-ligands as predictive and prognostic biomarkers in blood in breast cancer. Further exploration in large well-designed studies is needed.
Topics: Biomarkers, Tumor; Breast Neoplasms; ErbB Receptors; Female; Humans; Ligands; Predictive Value of Tests; Prognosis
PubMed: 29194036
DOI: 10.1515/cclm-2017-0592