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Experimental and Therapeutic Medicine Apr 2018Liver cancer is an aggressive malignancy with a very high fatality rate. Although megestrol acetate (MA) and arsenic trioxide (ATO) have shown an antitumor effect in...
Liver cancer is an aggressive malignancy with a very high fatality rate. Although megestrol acetate (MA) and arsenic trioxide (ATO) have shown an antitumor effect in liver cancer cells, the therapeutic benefits of MA or ATO alone in patients with liver cancer were limited. The aim of the present study was to elucidate whether the co-treatment of MA/ATO could enhance antitumor efficacy in liver cancer cell lines (Hep G2 and BEL 7402) and explore the underlying anti-cancer mechanisms. The cell viability, apoptotic response and expression levels of associated proteins were detected by Cell Counting Kit-8 assay, flow cytometry and western blotting, respectively. An xenograft model in nude mice bearing a Hep G2 tumor was used to estimate tumor growth . Co-treatment with MA/ATO markedly improved the inhibition of cell viability, enhanced apoptosis, and increased the phosphorylation of p38, c-Jun N-terminal kinase 1/2 and extracellular signal-regulated kinase 1/2 on liver cancer cell lines. Furthermore, the tumor growth in the murine Hep G2 cancer xenograft model was significantly inhibited by combined treatment with MA/ATO. The results indicated that MA/ATO combined treatment enhanced antitumor efficacy and possessed potential application for treating liver cancer.
PubMed: 29581752
DOI: 10.3892/etm.2018.5905 -
Breast (Edinburgh, Scotland) Apr 2013The proportion of elderly women in the population is rising, and in tandem, the incidence of breast cancer rises with age. Because of health and tolerability concerns,... (Review)
Review
The proportion of elderly women in the population is rising, and in tandem, the incidence of breast cancer rises with age. Because of health and tolerability concerns, as well as life expectancy, physicians may be reluctant to advise a standard treatment regimen for elderly patients with metastatic breast cancer. To elucidate this issue, we performed a literature review of clinical studies that included women with metastatic breast cancer who were over the age of 65. Our results show that although little clinical evidence exists, what is available suggests that standard treatment is tolerated and beneficial for patients meeting certain criteria. A geriatric assessment may identify specific patient groups (independent, dependent, or frail) and thereby guide treatment. Treatment recommendations for elderly patients with metastatic breast cancer are sparse, although first-line endocrine treatment, usually aromatase inhibitors or tamoxifen, is recommended for hormone-sensitive disease. In general, the evidence from clinical studies suggests that aromatase inhibitors are more effective than either tamoxifen or megestrol acetate as first- or second-line treatment in postmenopausal women with metastatic breast cancer. Ultimately, quality of life, treatment effects, and comorbidities are important aspects in this population and may guide treatment choice. To provide evidence-based treatment guidance, future clinical trials should include more patients over the age of 65 years.
Topics: Aged, 80 and over; Anastrozole; Androstadienes; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Comorbidity; Disease Management; Disease Progression; Drug Therapy, Combination; Female; Geriatric Assessment; Health Status; Humans; Letrozole; Life Expectancy; Nitriles; Prognosis; Quality of Life; Treatment Outcome; Triazoles
PubMed: 23321585
DOI: 10.1016/j.breast.2012.12.015 -
Pharmaceuticals (Basel, Switzerland) Jan 2022In this study, the effect of Cremophor RH 40 (CR 40) classic micelles and Soluplus (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system...
In this study, the effect of Cremophor RH 40 (CR 40) classic micelles and Soluplus (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system containing megestrolacetate (MGA). Using a risk assessment-based approach on the formulation via melt technology resulted in the formation of these granules, presented as the dosage, with proper particle size and flow characteristics. Due to the application of a eutectic carrier base composition, gentle process conditions were reached, retaining the crystalline structure of the carrier system and allowing for the proper distribution of MGA in the granules. The increased water solubility (0.111 mg/mL to 2.154 mg/mL), and the decreased nano particle size (102.27 nm) with uniform distribution (polydispersity index of 0.259) and colloid stability (zeta potential of -12.99 mV) resulted in SP polymeric micelles prevailing over CR 40 micelles in this gastric dissolution study, performed in biorelevant fasted and fed state drug-release media. Mathematical characterization and kinetic model fitting supported the fast drug-release mechanism of polymeric micelles over micelles. The value-added polymeric micelle-containing formulation developed can be successfully administered perorally and the enhanced drug release offers the possibility of greater drug absorption in the gastrointestinal tract.
PubMed: 35215226
DOI: 10.3390/ph15020113 -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
ESC Heart Failure Jun 2015As life expectancy increases, muscle wasting is becoming a more and more important public health problem. This review summarizes the current knowledge of... (Review)
Review
PURPOSE
As life expectancy increases, muscle wasting is becoming a more and more important public health problem. This review summarizes the current knowledge of pathophysiological mechanisms underlying muscle loss in ageing and chronic diseases such as heart failure and discusses evolving interventional strategies.
RECENT FINDINGS
Loss of skeletal muscle mass and strength is a common phenomenon in a wide variety of disorders associated with ageing and morbidity-associated catabolic conditions such as chronic heart failure. Muscle wasting in ageing but otherwise healthy human beings is referred to as sarcopenia. Unlike cachexia in advanced stages of chronic heart failure, muscle wasting per se is not necessarily associated with weight loss. In this review, we discuss pathophysiological mechanisms underlying muscle loss in sarcopenia and cachexia, highlight similarities and differences of both conditions, and discuss therapeutic targets and possible treatments, such as exercise training, nutritional support, and drugs. Candidate drugs to treat muscle wasting disease include myostatin antagonists, ghrelin agonists, selective androgen receptor molecules, megestrol acetate, activin receptor antagonists, espindolol, and fast skeletal muscle troponin inhibitors.
SUMMARY
Present approaches to muscle wasting disease include exercise training, nutritional support, and drugs, although particularly the latter remain currently restricted to clinical studies. Optimizing skeletal muscle mass and function in ageing and chronic illness including heart failure is one of the chapters that are far from finished and gains future potential for new therapeutic interventions to come.
PubMed: 28834653
DOI: 10.1002/ehf2.12033 -
International Journal of Women's Health 2014Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that... (Review)
Review
Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that 15%-25% of women will be diagnosed before menopause. As more women choose to defer childbearing until later in life, the feasibility and safety of fertility-sparing EC management have been increasingly studied. Definitive treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women who wish to maintain their reproductive potential. However, the consideration of conservative management carries the oncologic risks of unstaged EC and the risk of missing a synchronous ovarian cancer. It is further complicated by the lack of consensus regarding the initial assessment, treatment, and surveillance. Conservative treatment with progestins has been shown to be a feasible and safe fertility-sparing approach for women with low grade, early stage EC with no myometrial invasion. The two most commonly adopted regimens are medroxyprogesterone acetate at 500-600 mg daily and megestrol acetate at 160 mg daily for a minimum of 6-9 months, with initial response rates commonly reported between 60% and 80% and recurrence rates between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have recently been reported as alternative approaches to progestin therapy alone. However, limited efficacy and safety data exist. Live birth rates after progestin therapy have typically been reported around 30%; however, when focusing only on those who do pursue fertility after successful treatment, the live birth rates were found to be higher than 60%. Assisted reproductive technology has been associated with a higher live birth rate compared with spontaneous conception, most likely reflecting the presence of infertility at baseline. Close follow-up is of paramount importance, and definitive treatment after completion of childbearing is advised.
PubMed: 25114594
DOI: 10.2147/IJWH.S47232 -
British Medical Journal Dec 1976
Topics: Chemistry, Pharmaceutical; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Drug Combinations
PubMed: 1009397
DOI: 10.1136/bmj.2.6051.1560-b -
The Cochrane Database of Systematic... Oct 2009Endocrine therapy removes the influence of oestrogen on breast cancer cells and so hormonal treatments such as tamoxifen, megestrol acetate and medroxyprogesterone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endocrine therapy removes the influence of oestrogen on breast cancer cells and so hormonal treatments such as tamoxifen, megestrol acetate and medroxyprogesterone acetate have been in use for many years for advanced breast cancer. Aromatase inhibitors (AIs) inhibit oestrogen synthesis in the peripheral tissues and have a similar tumour-regressing effect to other endocrine treatments. Aminoglutethimide was the first AI in clinical use and now the third generation AIs, anastrozole, exemestane and letrozole, are in current use. Randomised trial evidence on response rates and side effects of these drugs is still limited.
OBJECTIVES
To compare AIs to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women.
SEARCH STRATEGY
For this update, the Cochrane Breast Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) and relevant conference proceedings were searched (to 30 June 2008).
SELECTION CRITERIA
Randomised controlled trials in postmenopausal women comparing the effects of any AI versus other endocrine therapy, no endocrine therapy, or a different AI in the treatment of advanced (metastatic) breast cancer. Non-English language publications, comparisons of the same AI at different doses, AIs used as neoadjuvant treatment, or outcomes not related to tumour response were excluded.
DATA COLLECTION AND ANALYSIS
Data from published trials were extracted independently by two review authors and cross-checked by a third. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progression-free survival). Odds ratios (OR) were derived for objective response, clinical benefit, and toxicity.
MAIN RESULTS
Thirty-seven trials were identified, 31 of which were included in the main analysis of any AI versus any other treatment (11,403 women). No trials were excluded due to inadequate allocation concealment. The pooled estimate showed a significant survival benefit for treatment with an AI over other endocrine therapies (HR 0.90, 95% CI 0.84 to 0.97). A subgroup analysis of the three commonly prescribed AIs (anastrozole, exemestane, letrozole) also showed a similar survival benefit (HR 0.88, 95% CI 0.80 to 0.96). There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole.AIs have a different toxicity profile to other endocrine therapies. For those currently prescribed, and for all AIs combined, they had similar levels of hot flushes and arthralgia; increased risks of rash, nausea, diarrhoea and vomiting; but a 71% decreased risk of vaginal bleeding and 47% decrease in thromboembolic events compared with other endocrine therapies.
AUTHORS' CONCLUSIONS
In women with advanced (metastatic) breast cancer, aromatase inhibitors including those in current clinical use show a survival benefit when compared to other endocrine therapy.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Neoplasms, Hormone-Dependent; Postmenopause; Randomized Controlled Trials as Topic
PubMed: 19821307
DOI: 10.1002/14651858.CD003370.pub3 -
Clinical Nutrition (Edinburgh, Scotland) Feb 2024Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy... (Review)
Review
Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.
Topics: Humans; Aged; Cachexia; Anorexia; Megestrol Acetate; Neoplasms; Appetite Stimulants
PubMed: 38237369
DOI: 10.1016/j.clnu.2024.01.009 -
Kidney International Aug 2006Anorexia, defined as the loss of the desire to eat, is relatively common in hemodialysis (HD) patients, occurring in one-third of cases. The pathogenesis is essentially... (Review)
Review
Anorexia, defined as the loss of the desire to eat, is relatively common in hemodialysis (HD) patients, occurring in one-third of cases. The pathogenesis is essentially unknown. It has been proposed that uremic toxins as middle molecules, inflammation, altered amino-acid pattern, leptin, ghrelin, and neuropeptide Y are involved. Anorexia reduces oral energy and protein intakes, thus contributing to the development of malnutrition and cachexia. Unquestionably, it contributes to poor quality of life. The clinical relevance of anorexia as an independent prognostic factor in HD patients is a matter of debated issue. The treatment of this debilitating condition is based on a therapeutic strategy which may include daily dialysis sessions and nutritional counseling. Normalization of plasma branched-chain amino acids through branched-chain amino acids supplementation may decrease anorexia and improve energy and protein intake. The role of megestrol acetate as appetite stimulant needs to be validated through adequate randomized trials. Subcutaneous ghrelin administration and melanocortin-receptor antagonists appear promising therapeutic interventions.
Topics: Anorexia; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 16775598
DOI: 10.1038/sj.ki.5001572