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Journal of Plastic, Reconstructive &... Jun 2022Insufficient and inconsistent survival is a significant shortcoming of fat grafts. Reportedly, megestrol acetate (MA) could induce proliferation, migration, and...
Insufficient and inconsistent survival is a significant shortcoming of fat grafts. Reportedly, megestrol acetate (MA) could induce proliferation, migration, and adipogenic differentiation of adipose-derived stem cells in vitro. Thus, we tested whether MA could promote fat graft survival in a rat model. Twenty-eight Sprague-Dawley rats (8 weeks old, male) were divided into two groups: experimental (MA group, n = 14) and control (n = 14). The inguinal fat pad (1 g) was extracted en bloc and re-implanted under the scalp in both groups. MA (100 mg/kg/day) was administered orally for 14 postoperative days in the experimental group. After 6 weeks, the volume and weight of the grafted fat were measured. Histologic examination with hematoxylin and eosin (HE) and real-time polymerase chain reaction (PCR) for vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and CCAAT/enhancer-binding protein alpha (C/EBP-α) were performed. Perilipin staining was performed to check the viability of grafted fat. Graft fat volume was greater in the MA group, compared with that in the control (P = 0.023). The MA group also had more viable cells, including more adipocytes, and less fibrosis or vacuoles than the control on HE and perilipin staining. MA upregulated the expression of FGF2 (P<0.001), VEGF (P = 0.008), and C/EBP-α (P = 0.002) at the second postoperative week. MA increased survival of grafted fat in an animal model. Increased vascularization and adipogenesis were related to these results. Further human clinical trials are necessary to evaluate adjunctive oral administration of MA after fat grafting to promote graft survival.
Topics: Adipose Tissue; Administration, Oral; Animals; Fibroblast Growth Factor 2; Graft Survival; Humans; Male; Megestrol Acetate; Perilipins; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A
PubMed: 35125304
DOI: 10.1016/j.bjps.2022.01.004 -
Nanoemulsions Containing Megestrol Acetate: Development, Characterization, and Stability Evaluation.AAPS PharmSciTech May 2022Many active pharmaceutical ingredients (API) are poorly soluble in water and their low oral bioavailability is a major hindrance to their potential use. Megestrol...
Many active pharmaceutical ingredients (API) are poorly soluble in water and their low oral bioavailability is a major hindrance to their potential use. Megestrol acetate (MGA) is insoluble in water and its oral absorption is limited and considerably affected by food. Nanoemulsions (NEs) can be used as effective oral drug delivery systems where the hydrophobic API is loaded into the oil phase. In this study, MGA-loaded NEs were prepared based on the spontaneous emulsification technique. The effects of different excipients such as ethanol, Tween 80, Lipoid E80, and medium-chain triglyceride (MCT) on the NEs characterization were investigated. The experimental results indicated that optimum MGA-loaded NEs (F20) were nanometer-sized droplets (166.9 ± 3.0 nm) with negative zeta potential (-12.2 ± 1.1 mV). The effect of polyvinylpyrrolidone (PVP) on characteristic properties of F20 was also evaluated. On the selected NEs, in vitro dissolution tests and stability studies in various mediums and storage conditions were performed. The encapsulation efficiency of NEs were > 99%. The overall droplet size of F20 and PVP-2 (PVP-coated NEs) remained relatively stable as the pH changed from 1.2 to 6.8. It was determined that F20 and PVP-2 remained stable at 4°C until 12 weeks and had higher cytotoxicity on MCF-7 cells. To conclude, droplet size, surface charge, and stability are important properties for NEs to have sufficient effectiveness. In this study, alternative oral NEs of low-solubility drug MGA were developed considering the above features.
Topics: Emulsions; Humans; Megestrol Acetate; Polysorbates; Solubility; Water
PubMed: 35538251
DOI: 10.1208/s12249-022-02289-7 -
Gynecologic Oncology Jul 2023To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.
OBJECTIVE
To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH).
METHODS
This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated.
RESULTS
The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints.
CONCLUSIONS
LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial.
FUNDING
This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www.
CLINICALTRIALS
gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.
Topics: Pregnancy; Humans; Female; Levonorgestrel; Endometrial Hyperplasia; Megestrol Acetate; Prospective Studies; China; Fertility; Intrauterine Devices, Medicated
PubMed: 37182434
DOI: 10.1016/j.ygyno.2023.05.001 -
Frontiers in Oncology 2022The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients...
BACKGROUND
The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.
STUDY DESIGN
Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".
RESULTS
A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.
CONCLUSIONS
Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.
PubMed: 36185260
DOI: 10.3389/fonc.2022.965029 -
The European Journal of Contraception &... Oct 2022
Topics: Chlormadinone Acetate; Contraceptives, Oral, Combined; Female; Humans; Male; Megestrol; Meningeal Neoplasms; Meningioma
PubMed: 35997041
DOI: 10.1080/13625187.2022.2114792 -
Conservatively treated endometrial intraepithelial neoplasia/cancer: Risk of intrauterine synechiae.Journal of Gynecology Obstetrics and... May 2021To determine whether progestin type or number of dilation and curettage procedures (D&Cs) were associated with intrauterine synechiae (IS) or pregnancy outcomes in...
INTRODUCTION
To determine whether progestin type or number of dilation and curettage procedures (D&Cs) were associated with intrauterine synechiae (IS) or pregnancy outcomes in patients conservatively treated for endometrial intraepithelial neoplasia (EIN) or endometrial cancer (EC).
MATERIALS AND METHODS
We evaluated patients conservatively treated for EIN or EC from 2000 to 2017 at an academic center. IS were identified hysteroscopically. We calculated proportions for categorical variables and tested associations between D&C number, progestin, and pregnancy outcomes using Pearson chi-squared and Fisher's exact tests. A post-hoc power analysis indicated sufficient power to detect livebirth.
RESULTS
We analyzed 54 patients, 15 with EIN (28 %) and 39 with EC (72 %), with a mean age of 34 ± 1.2 years. Progestin treatment types included megestrol acetate (MA) (n = 24), MA with levonorgestrel intrauterine device (LngIUD) (n = 10), MA followed by LngIUD (n = 3), and LngIUD alone (n = 6). Mean number of D&Cs was 3.9 ± 0.9. Overall, 53 subjects underwent hysteroscopy; 10 (19 %) had IS. When D&Cs were grouped into 0-2, 3-4 and ≥5, each increase in D&C group had a 2.9 higher odds of IS (OR: 2.91, p = 0.04, CI: 1.05-10.02). LngIUD was associated with a nonsignificant 46 % decrease in the odds of IS (OR: 0.54, p = 0.66, CI: 0.08-2.87). Twenty-two women attempted pregnancy; 14 women achieved a total of 20 pregnancies and 9 women had total of 15 livebirths (41 % livebirth rate). The number of D&Cs and progestin treatment type were not associated with pregnancy outcomes.
DISCUSSION
Among 54 patients conservatively treated for EC/EIN, nearly 20 % developed IS. However, hysteroscopic and/or fertility treatments may improve pregnancy outcomes.
Topics: Adult; Carcinoma in Situ; Conservative Treatment; Contraceptive Agents, Female; Dilatation and Curettage; Endometrial Neoplasms; Female; Gynatresia; Humans; Hysteroscopy; Intrauterine Devices, Medicated; Levonorgestrel; Live Birth; Megestrol Acetate; Pregnancy; Pregnancy Outcome; Progestins; Retrospective Studies; Risk
PubMed: 33022448
DOI: 10.1016/j.jogoh.2020.101930 -
International Journal of Molecular... Oct 2021Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat... (Review)
Review
Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.
Topics: Adult; Endometrial Neoplasms; Female; Fertility; Fertility Preservation; Humans; Medroxyprogesterone Acetate; Myometrium; Neoplasm Staging; Progestins; Quality of Life
PubMed: 34769256
DOI: 10.3390/ijms222111825 -
Experimental and Therapeutic Medicine Jan 2023Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are...
Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are limited therapeutic options for this syndrome. Previous evidence has demonstrated that increasing adipose tissue may improve quality of life and survival outcomes in cachexia. Cisplatin, as a chemotherapy drug, also causes cachexia during antitumor therapy due to its adverse effects. To establish a rat model of cachexia, the animals were intraperitoneally treated with cisplatin at doses of 1, 2 and 3 mg/kg, and the rats that responded to cisplatin at the optimal dose were used to test the effect of nomegestrol acetate (NOMAc). Rats that were assessed to be sensitive to cisplatin were randomly grouped and intragastrically administered vehicle, 5 or 10 mg/kg megestrol acetate (MA) or 2.5, 5 or 10 mg/kg NOMAc. The body weights and food consumption of the rats were assessed. Serum IL-6 and TNF-α levels were assessed using ELISA. The protein expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), peroxisome proliferator activated receptor γ (PPARγ), fatty acid synthase (FASN) and sterol regulatory element-binding protein-1 (SREBP-1) from inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) were evaluated using western blotting. The optimal way to establish a chemotherapy-induced rat model of cachexia demonstrated in the present study was to intraperitoneally administer the rats with 2 mg/kg cisplatin for 3 consecutive days. NOMAc (2.5, 5 mg/kg) and MA (10 mg/kg) were able to significantly ameliorate the loss of body weight in the cisplatin-induced cachectic rats. NOMAc significantly reduced the serum levels of TNF-α at 10 mg/kg. Morphologically, iWAT atrophy, with a remarkable reduction in adipocyte volume, was observed in the cisplatin-induced cachectic rats, but the effects were reversed by administering 5, 10 mg/kg NOMAc or 10 mg/kg MA. Furthermore, 2.5 mg/kg NOMAc markedly reduced the protein expression levels of the lipolysis genes HSL and ATGL, and 5 mg/kg NOMAc markedly enhanced the protein expression levels of adipogenesis genes, including FASN, SREBP-1 and PPARγ in iWAT but not in eWAT. NOMAc was demonstrated to improve cachexia at lower doses compared with MA. Overall, NOMAc is likely to be a promising candidate drug for ameliorating cancer cachexia induced by cisplatin.
PubMed: 36561625
DOI: 10.3892/etm.2022.11723 -
Frontiers in Genetics 2022This study aimed to screen potential drugs targeting a new prognostic gene signature associated with proliferation in hepatocellular carcinoma (HCC). CRISPR Library...
This study aimed to screen potential drugs targeting a new prognostic gene signature associated with proliferation in hepatocellular carcinoma (HCC). CRISPR Library and TCGA datasets were used to explore differentially expressed genes (DEGs) related to the proliferation of HCC cells. Differential gene expression analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct a prognostic gene signature. Then the predictive power of the gene signature was validated in the TCGA and ICGC datasets. Furthermore, potential drugs targeting this gene signature were screened. A total of 640 DEGs related to HCC proliferation were identified. Using univariate Cox analysis and random forest algorithm, 10 hub genes were screened. Subsequently, using multiplex combinatorial screening, five hub genes (FARSB, NOP58, CCT4, DHX37 and YARS) were identified. Taking the median risk score as a cutoff value, HCC patients were divided into high- and low-risk groups. Kaplan-Meier analysis performed in the training set showed that the overall survival of the high-risk group was worse than that of the low-risk group ( < 0.001). The ROC curve showed a good predictive efficiency of the risk score (AUC > 0.699). The risk score was related to gene mutation, cancer cell stemness and immune function changes. Prediction of immunotherapy suggetsted the IC50s of immune checkpoint inhibitors including A-443654, ABT-888, AG-014699, ATRA, AUY-922, and AZ-628 in the high-risk group were lower than those in the low-risk group, while the IC50s of AMG-706, A-770041, AICAR, AKT inhibitor VIII, Axitinib, and AZD-0530 in the high-risk group were higher than those in the low-risk group. Drug sensitivity analysis indicated that FARSB was positively correlated with Hydroxyurea, Vorinostat, Nelarabine, and Lomustine, while negatively correlated with JNJ-42756493. DHX37 was positively correlated with Raltitrexed, Cytarabine, Cisplatin, Tiotepa, and Triethylene Melamine. YARS was positively correlated with Axitinib, Fluphenazine and Megestrol acetate. NOP58 was positively correlated with Vorinostat and 6-thioguanine. CCT4 was positively correlated with Nerabine. The five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC.
PubMed: 35836576
DOI: 10.3389/fgene.2022.900380 -
Supportive Care in Cancer : Official... Apr 2024We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration.
PURPOSE
We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration.
METHODS
We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships.
RESULTS
The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients.
CONCLUSION
The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.
Topics: Humans; Anorexia; Male; Female; Middle Aged; Quality of Life; Neoplasms; Surveys and Questionnaires; Antineoplastic Agents; Aged; Adult; Megestrol Acetate; Nutrition Assessment; Appetite Stimulants; Taste
PubMed: 38644409
DOI: 10.1007/s00520-024-08499-y