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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 -
The Cochrane Database of Systematic... 2003Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003). Unfortunately the low oestrogen state that they induce is associated with adverse effects including an acceleration in bone mineral density (BMD) loss.
OBJECTIVES
To determine the effect of treatment with gonadotrophin-releasing hormone analogues (GnRHas) on the bone mineral density of women with endometriosis, compared to placebo, no treatment, or other treatments for endometriosis, including GnRHas with add-back therapy.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials (23rd October 2002) and the Cochrane Central Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 - March Week 2 2003). We also searched the reference lists of articles and contacted researchers in the field.
SELECTION CRITERIA
Prospective, randomised controlled studies of the use of GnRHas for the treatment of women with endometriosis were considered, where bone density measurements were an end point. The control arm of the studies was either placebo, no treatment, another medical therapy for endometriosis, or GnRHas with add-back therapy.
DATA COLLECTION AND ANALYSIS
Two reviewers (JF and MS) independently assessed trial quality and extracted data. Study authors were contacted for additional information.
MAIN RESULTS
Thirty studies involving 2,391 women were included, however only 15, involving 910 women, could be included in the meta-analysis. The meta-analysis showed that danazol and progesterone + oestrogen add-back are protective of BMD at the lumbar spine both during treatment and for up to six and twelve months after treatment, respectively. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after six months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after six months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRH analogues (SMD 0.15, 95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back, that is oestrogen + progesterone or oestrogen only, there was a significantly bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21). These numbers reflect the absolute value measurements at the lumbar spine after six months of treatment. Due to the small number of studies in the comparison we are unable to conclude whether calcium-regulating agents are protective. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill (OCP) or progestagens were identified.
REVIEWER'S CONCLUSIONS
Both danazol and progesterone + oestrogen add-back have been shown to be protective of BMD, while on treatment and up to six and 12 months later, respectively. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Studies of danazol versus GnRHa did not report long-term follow-up. The significant side effects associated with danazol limit its use.
Topics: Bone Density; Danazol; Endometriosis; Estrogen Antagonists; Female; Femur Neck; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Lumbar Vertebrae; Manipulation, Spinal; Progesterone
PubMed: 14583930
DOI: 10.1002/14651858.CD001297 -
The Cochrane Database of Systematic... Jul 2014Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a wide range of drugs that can inhibit labour to prolong pregnancy. This may gain time to allow the fetus to mature further before being born, permit antenatal corticosteroid administration for lung maturation, and allow time for intra-uterine transfer to a hospital with neonatal intensive care facilities. However, some tocolytic drugs are associated with severe side effects. Combinations of tocolytic drugs may be more effective over single tocolytic agents or no intervention, without adversely affecting the mother or neonate.
OBJECTIVES
To assess the effects on maternal, fetal and neonatal outcomes of any combination of tocolytic drugs for the treatment of preterm labour when compared with any other treatment, no treatment or placebo.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials comparing a combination of tocolytic agents, administered by any route or any dose, for inhibiting preterm labour versus any other treatment (including other combinations of tocolytics or single tocolytics), no intervention or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study reports for eligibility, carried out data extraction and assessed risk of bias.
MAIN RESULTS
Eleven studies met our inclusion criteria. Two studies did not report any outcome data relevant to the review, so the results of the review are based on nine trials that contributed data. Primary outcomes were perinatal mortality, serious maternal or infant outcomes, adverse drug reactions, birth before 48 hours of trial entry, birth before 34 weeks' gestation and preterm neonates delivered without a full course of antenatal steroids completed 24 hours before birth. The quality of evidence in included trials was mixed; only three of the trials were placebo controlled.The included trials examined seven different comparisons: intravenous (IV) ritodrine plus oral or IV magnesium (sulphate or gluconate) versus IV ritodrine alone (three trials, 231 women); IV ritodrine plus indomethacin suppositories versus IV ritodrine alone (one trial, 208 women); IV ritodrine plus vaginal progesterone versus IV ritodrine alone (one trial, 83 women); IV hexoprenaline sulphate plus IV magnesium hydrochloride versus IV hexoprenaline sulphate alone (one trial, 24 women); IV fenoterol plus oral naproxen versus IV fenoterol alone (one trial, 72 women); oral pentoxifylline plus IV magnesium sulphate plus IV fenoterol versus IV magnesium sulphate plus IV fenoterol (one trial, 125 women); and, IV terbutaline plus oral metoprolol versus IV terbutaline alone (one trial, 17 women). Few studies with small numbers of women were available for each comparison, hence very little data were pooled in meta-analysis. In all trials, not many of the primary outcomes were reported.Three trials examined intravenous (IV) ritodrine plus IV or oral magnesium (sulphate or gluconate) compared with IV ritodrine alone. One study, with 41 women, reported more adverse drug reactions in the group receiving the combined tocolytics (risk ratio (RR) 7.79, 95% confidence interval (CI) 1.11 to 54.80). Two trials reported discontinuation of therapy due to severe side effects (results were not combined due to high statistical heterogeneity, I² = 83%); one trial reported increased severe side effects in the group receiving IV ritodrine alone (RR 7.79, 95% CI 1.11 to 54.80, 41 women); in the other trial there was no clear difference between groups (RR 0.23, 95% CI 0.03 to 1.97, 107 women). Other primary outcomes were not reported.One trial assessed IV ritodrine plus indomethacin suppositories versus IV ritodrine alone. There were no significant differences between groups for perinatal mortality or serious neonatal morbidity. Results for other primary outcomes were not reported.There were no significant differences between groups receiving IV ritodrine plus vaginal progesterone compared with IV ritodrine alone for most outcomes reported, although the latency period (time from recruitment to delivery) was increased in the group receiving the combination of tocolytics.For other combinations of tocolytic agents, primary outcomes were rarely reported and for secondary outcomes results did not demonstrate differences between groups.
AUTHORS' CONCLUSIONS
It is unclear whether a combination of tocolytic drugs for preterm labour is more advantageous for women and/or newborns due to a lack of large, well-designed trials including the outcomes of interest. There are no trials of combination regimens using widely used tocolytic agents, such as calcium channel blockers (nifedipine) and/or oxytocin receptor antagonists (atosiban). Further trials are needed before specific conclusions on use of combination tocolytic therapy for preterm labour can be made.
Topics: Drug Therapy, Combination; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents
PubMed: 25010869
DOI: 10.1002/14651858.CD006169.pub2 -
Fertility and Sterility Dec 2008To investigate the effect of luteal E(2) supplementation on the pregnancy rate of IVF/intracytoplasmic sperm injection (ICSI) cycles. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the effect of luteal E(2) supplementation on the pregnancy rate of IVF/intracytoplasmic sperm injection (ICSI) cycles.
DESIGN
A systematic review and meta-analysis of all the randomized controlled trials (RCTs).
SETTING
Tertiary referral center for reproductive medicine and IVF.
PATIENT(S)
Women undergoing IVF or ICSI using the GnRH agonist or GnRH antagonist protocol with hMG or FSH for controlled ovarian hyperstimulation.
INTERVENTION(S)
Progesterone (P4) alone or combined with estradiol valerate for luteal phase support.
MAIN OUTCOME MEASURE(S)
Pregnancy and clinical pregnancy rates per ET.
RESULT(S)
An electronic search was conducted targeting all reports published between January 1960 and March 2007. Ten RCTs met the criteria for inclusion in the meta-analysis. There were no statistically significant differences with regard to the main outcome measures, ongoing pregnancy rate per ET, or implantation rate between the group of women who had combined E(2) and P4 therapy and those who had P4 supplementation alone.
CONCLUSION(S)
The addition of E(2) to P4 for luteal phase support in IVF/ICSI cycles has no beneficial effect on pregnancy rates. The data in the literature are, however, limited and heterogeneous, precluding the extraction of clear and definite conclusions. A large multicenter, properly designed RCT is needed to further clarify the role of luteal E(2) supplementation in IVF.
Topics: Adult; Drug Therapy, Combination; Embryo Implantation; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Luteal Phase; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 18178194
DOI: 10.1016/j.fertnstert.2007.10.053 -
BMC Cancer May 2024Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN)...
BACKGROUND
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC.
METHODS
MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens.
RESULTS
Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics.
CONCLUSIONS
The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.
Topics: Humans; Cyclin-Dependent Kinase 4; Breast Neoplasms; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Female; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Receptors, Estrogen; Receptors, Progesterone; Progression-Free Survival
PubMed: 38783218
DOI: 10.1186/s12885-024-12269-8 -
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 -
The Cochrane Database of Systematic... May 2017Among subfertile women undergoing assisted reproductive technology (ART), hormone pills given before ovarian stimulation may improve outcomes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among subfertile women undergoing assisted reproductive technology (ART), hormone pills given before ovarian stimulation may improve outcomes.
OBJECTIVES
To determine whether pretreatment with the combined oral contraceptive pill (COCP) or with a progestogen or oestrogen alone in ovarian stimulation protocols affects outcomes in subfertile couples undergoing ART.
SEARCH METHODS
We searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, The Cochrane Central Register Studies Online, MEDLINE, Embase, CINAHL and PsycINFO. We also searched the reference lists of relevant articles and registers of ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of hormonal pretreatment in women undergoing ART.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth or ongoing pregnancy and pregnancy loss.
MAIN RESULTS
We included 29 RCTs (4701 women) of pretreatment with COCPs, progestogens or oestrogens versus no pretreatment or alternative pretreatments, in gonadotrophin-releasing hormone (GnRH) agonist or antagonist cycles. Overall, evidence quality ranged from very low to moderate. The main limitations were risk of bias and imprecision. Most studies did not describe their methods in adequate detail. Combined oral contraceptive pill versus no pretreatmentWith antagonist cycles in both groups the rate of live birth or ongoing pregnancy was lower in the pretreatment group (OR 0.74, 95% CI 0.58 to 0.95; 6 RCTs; 1335 women; I = 0%; moderate quality evidence). There was insufficient evidence to determine whether the groups differed in rates of pregnancy loss (OR 1.36, 95% CI 0.82 to 2.26; 5 RCTs; 868 women; I = 0%; moderate quality evidence), multiple pregnancy (OR 2.21, 95% CI 0.53 to 9.26; 2 RCTs; 125 women; I = 0%; low quality evidence), ovarian hyperstimulation syndrome (OHSS; OR 0.98, 95% CI 0.28 to 3.40; 2 RCTs; 642 women; I = 0%, low quality evidence), or ovarian cyst formation (OR 0.47, 95% CI 0.08 to 2.75; 1 RCT; 64 women; very low quality evidence).In COCP plus antagonist cycles versus no pretreatment in agonist cycles, there was insufficient evidence to determine whether the groups differed in rates of live birth or ongoing pregnancy (OR 0.89, 95% CI 0.64 to 1.25; 4 RCTs; 724 women; I = 0%; moderate quality evidence), multiple pregnancy (OR 1.36, 95% CI 0.85 to 2.19; 4 RCTs; 546 women; I = 0%; moderate quality evidence), or OHSS (OR 0.63, 95% CI 0.20 to 1.96; 2 RCTs; 290 women, I = 0%), but there were fewer pregnancy losses in the pretreatment group (OR 0.40, 95% CI 0.22 to 0.72; 5 RCTs; 780 women; I = 0%; moderate quality evidence). There were no data suitable for analysis on ovarian cyst formation.One small study comparing COCP versus no pretreatment in agonist cycles showed no clear difference between the groups for any of the reported outcomes. Progestogen versus no pretreatmentAll studies used the same protocol (antagonist, agonist or gonadotrophins) in both groups. There was insufficient evidence to determine any differences in rates of live birth or ongoing pregnancy (agonist: OR 1.35, 95% CI 0.69 to 2.65; 2 RCTs; 222 women; I = 24%; low quality evidence; antagonist: OR 0.67, 95% CI 0.18 to 2.54; 1 RCT; 47 women; low quality evidence; gonadotrophins: OR 0.63, 95% CI 0.09 to 4.23; 1 RCT; 42 women; very low quality evidence), pregnancy loss (agonist: OR 2.26, 95% CI 0.67 to 7.55; 2 RCTs; 222 women; I = 0%; low quality evidence; antagonist: OR 0.36, 95% CI 0.06 to 2.09; 1 RCT; 47 women; low quality evidence; gonadotrophins: OR 1.00, 95% CI 0.06 to 17.12; 1 RCT; 42 women; very low quality evidence) or multiple pregnancy (agonist: no data available; antagonist: OR 1.05, 95% CI 0.06 to 17.76; 1 RCT; 47 women; low quality evidence; gonadotrophins: no data available). Three studies, all using agonist cycles, reported ovarian cyst formation: rates were lower in the pretreatment group (OR 0.16, 95% CI 0.08 to 0.32; 374 women; I = 1%; moderate quality evidence). There were no data on OHSS. Oestrogen versus no pretreatmentIn antagonist or agonist cycles, there was insufficient evidence to determine whether the groups differed in rates of live birth or ongoing pregnancy (antagonist versus antagonist: OR 0.79, 95% CI 0.53 to 1.17; 2 RCTs; 502 women; I = 0%; low quality evidence; antagonist versus agonist: OR 0.88, 95% CI 0.51 to 1.50; 2 RCTs; 242 women; I = 0%; very low quality evidence), pregnancy loss (antagonist versus antagonist: OR 0.16, 95% CI 0.02 to 1.47; 1 RCT; 49 women; very low quality evidence; antagonist versus agonist: OR 1.59, 95% CI 0.62 to 4.06; 1 RCT; 220 women; very low quality evidence), multiple pregnancy (antagonist versus antagonist: no data available; antagonist versus agonist: OR 2.24, 95% CI 0.09 to 53.59; 1 RCT; 22 women; very low quality evidence) or OHSS (antagonist versus antagonist: no data available; antagonist versus agonist: OR 1.54, 95% CI 0.25 to 9.42; 1 RCT; 220 women). Ovarian cyst formation was not reported. Head-to-head comparisonsCOCP was compared with progestogen (1 RCT, 44 women), and with oestrogen (2 RCTs, 146 women), and progestogen was compared with oestrogen (1 RCT, 48 women), with an antagonist cycle in both groups. COCP in an agonist cycle was compared with oestrogen in an antagonist cycle (1 RCT, 25 women). Data were scant but there was no clear evidence that any of the groups differed in rates of live birth or ongoing pregnancy, pregnancy loss or other adverse events.
AUTHORS' CONCLUSIONS
Among women undergoing ovarian stimulation in antagonist protocols, COCP pretreatment was associated with a lower rate of live birth or ongoing pregnancy than no pretreatment. There was insufficient evidence to determine whether rates of live birth or ongoing pregnancy were influenced by pretreatment with progestogens or oestrogens, or by COCP pretreatment using other stimulation protocols. Findings on adverse events were inconclusive, except that progesterone pretreatment may reduce the risk of ovarian cysts in agonist cycles, and COCP in antagonist cycles may reduce the risk of pregnancy loss compared with no pretreatment in agonist cycles.
Topics: Contraceptives, Oral; Estrogens; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Progestins; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 28540977
DOI: 10.1002/14651858.CD006109.pub3 -
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 -
Journal of Gynecology Obstetrics and... Sep 2021To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically evaluate the effect of progestin-primed ovarian stimulation (PPOS) in in vitro fertilization (IVF)/oocyte intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in patients with poor ovarian response and to find an optimal ovulation induction protocol for such patients.
METHOD
A literature search of PubMed, Medline, EBSCO, Cochrane Library, Vip.com, CNKI, and the Wanfang database was conducted to find case-control studies of PPOS with medroxyprogesterone acetate and other traditional stimulation regimens for ovulation induction in patients with poor ovarian response. The period of time searched was from the database establishment to August 2020. Patients in the experimental group underwent PPOS and those in the control group underwent another program (e.g., the gonadotropin-releasing hormone antagonist protocol). RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of sixteen case-control studies (one of them is randomized controlled trial), with 4422 induction cycles, were included. All the included patients met the 2011 Bologna diagnostic criteria for poor ovarian response. The numbers of mature eggs, available embryos, optimal embryos, and the rate of cumulative pregnancies in the PPOS group were all better than those in the control group (P<0.05). There was a lower Serum luteinizing hormone on the day of human chorionic gonadotropin (HCG) injection and a lower rate of cycle cancellation in the PPOS group (P<0.05). No other differences between PPOS and other treatments were statistically significant.
CONCLUSION
PPOS can reduce the need for cycle cancellation, improve the follicles and embryos, and improve the pregnancy rate and thus, can present an effective choice for IVF/ICSI-ET in patients with poor ovarian response.
Topics: Adult; Case-Control Studies; Contraceptive Agents, Hormonal; Female; Humans; Medroxyprogesterone Acetate; Ovary; Ovulation Induction; Treatment Outcome
PubMed: 33387677
DOI: 10.1016/j.jogoh.2020.102049