scholarly journals Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Diana Hatoum ◽  
Eileen M. McGowan

There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients.In vitrostudies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I–III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlightingin vitroresearch and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer.

2007 ◽  
Vol 25 (14) ◽  
pp. 1882-1890 ◽  
Author(s):  
Diana Crivellari ◽  
Matti Aapro ◽  
Robert Leonard ◽  
Gunter von Minckwitz ◽  
Etienne Brain ◽  
...  

Screening and adjuvant postoperative therapies have increased survival among women with breast cancer. These tools are seldom applied in elderly patients, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Elderly breast cancer patients, even if in good medical health, were frequently excluded from adjuvant clinical trials. Women age 70 years who are fit actually have a median life expectancy of 15.5 years, ie, half of them will live much longer and will remain exposed for enough time to the potentially preventable risks of a relapse and specific death. In the last few years, a new concern about this issue has developed. Treatment now faces two major end points, as in younger women: to improve disease-free survival in the early stages, and to palliate symptoms in advanced disease. However, in both settings, the absolute benefit of treatment is critical because protecting quality of life and all its related aspects (especially functional status and independence), is crucial in older persons who have more limited life expectancy. Furthermore, the new hormonal compounds (aromatase inhibitors) and chemotherapeutic drugs (capecitabine, liposomal doxorubicin), are potentially less toxic than and equally as effective as older more established therapies. These new treatments bring new challenges including higher cost, and defining their benefit in elderly breast cancer must include an analysis of the cost/benefit ratio. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients both in the adjuvant and metastatic settings, a move that will take us from a prejudiced, age-based medicine to an evidence-based medicine.


Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 239-248 ◽  
Author(s):  
Anju Benny ◽  
Jaya Thomas

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Safaet Alam ◽  
Taslima Binte Kamal ◽  
Md. Moklesur Rahman Sarker ◽  
Jin-Rong Zhou ◽  
S. M. Abdur Rahman ◽  
...  

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1731
Author(s):  
Caomhán J. Lyons ◽  
Timothy O'Brien

Endothelial-colony-forming cells (ECFCs) are a population of progenitor cells which have demonstrated promising angiogenic potential both in vitro and in vivo. However, ECFCs from diabetic patients have been shown to be dysfunctional compared to ECFCs from healthy donors. Diabetes mellitus itself presents with many vascular co-morbidities and it has been hypothesized that ECFCs may be a potential cell therapy option to promote revascularisation in these disorders. While an allogeneic cell therapy approach would offer the potential of an ‘off the shelf’ therapeutic product, to date little research has been carried out on umbilical cord-ECFCs in diabetic models. Alternatively, autologous cell therapy using peripheral blood-ECFCs allows the development of a personalised therapeutic approach to medicine; however, autologous diabetic ECFCs are dysfunctional and need to be repaired so they can effectively treat diabetic co-morbidities. Many different groups have modified autologous diabetic ECFCs to improve their function using a variety of methods including pre-treatment with different factors or with genetic modification. While the in vitro and in vivo data from the literature is promising, no ECFC therapy has proceeded to clinical trials to date, indicating that more research is needed for a potential ECFC therapy in the future to treat diabetic complications.


Drug Research ◽  
2020 ◽  
Author(s):  
Saptarshi Chatterjee

AbstractRemdesivir is presently been considered as ‘molecule of hope’ to curb the menace of COVID19. Non-availability of any USFDA approved drug has led to several attempt of drug-repurposing and development of new therapeutic molecules. However, Remdesivir has been found to be effective against a broad range of virus including SARS, MERS and COVID 19 through in-vitro studies. Several clinical research attempt are presently being conducted showing promising result yet not conclusive. This review summarized all such clinical trials to critically appraise the usage of Remdesivir against COVID 19 along with the publications related to the results of the clinical studies. The present regulatory aspect i. e. Emergency Use Authorization (EYA) and information of molecule and plausible mechanism is also dealt.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
T. M. Hommels ◽  
R. S. Hermanides ◽  
B. Berta ◽  
E. Fabris ◽  
G. De Luca ◽  
...  

Abstract Background Several studies compared everolimus-eluting bioresorbable scaffolds (EE-BRS) with everolimus-eluting stents (EES), but only few assessed these devices in patients with diabetes mellitus. Aim To evaluate the safety and efficacy outcomes of all-comer patients with diabetes mellitus up to 2 years after treatment with EE-BRS or EES. Methods We performed a post hoc pooled analysis of patient-level data in diabetic patients who were treated with EE-BRS or EES in 3 prospective clinical trials: The ABSORB DM Benelux Study (NTR5447), TWENTE (NTR1256/NCT01066650) and DUTCH PEERS (NTR2413/NCT01331707). Primary endpoint of the analysis was target lesion failure (TLF): a composite of cardiac death, target vessel myocardial infarction or clinically driven target lesion revascularization. Secondary endpoints included major adverse cardiac events (MACE): a composite of all-cause death, any myocardial infarction or clinically driven target vessel revascularization, as well as definite or probable device thrombosis (ST). Results A total of 499 diabetic patients were assessed, of whom 150 received EE-BRS and 249 received EES. Total available follow-up was 222.6 patient years (PY) in the EE-BRS and 464.9 PY in the EES group. The adverse events rates were similar in both treatment groups for TLF (7.2 vs. 5.2 events per 100 PY, p = 0.39; adjusted hazard ratio (HR) = 1.48 (95% confidence interval (CI): 0.77–2.87), p = 0.24), MACE (9.1 vs. 8.3 per 100 PY, p = 0.83; adjusted HR = 1.23 (95% CI: 0.70–2.17), p = 0.47), and ST (0.9 vs. 0.6 per 100 PY, p > 0.99). Conclusion In this patient-level pooled analysis of patients with diabetes mellitus from 3 clinical trials, EE-BRS showed clinical outcomes that were quite similar to EES.


Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5240
Author(s):  
Koraljka Gall Trošelj ◽  
Ivana Samaržija ◽  
Marko Tomljanović ◽  
Renata Novak Kujundžić ◽  
Nikola Đaković ◽  
...  

Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status of publicly available data on curcumin clinical trials and a detailed presentation of results obtained so far with some curcumin formulations. Phenomena related to the observed effects of curcumin shown in clinical trials are presented, and its modifying effect on gut microbiota and metabolic reprogramming is discussed. Based on available data, there is a strong indication that curcumin and its metabolites present molecules that do not necessarily need to be abundant in order to act locally and benefit systemically. Future clinical studies should be designed in a way that will take that fact into consideration.


2007 ◽  
Vol 10 (1) ◽  
pp. 1-3 ◽  
Author(s):  
L. A. Schnaper ◽  
K. S. Hughes

Despite the fact that breast cancer is predominantly a disease of postmenopausal women, there have been no uniform recommendations for both locoregional and systemic therapy for women over 70. Until recently, older women have been excluded from clinical trials. This study is the first randomized trial that addresses the use of radiation therapy following lumpectomy in a favorable cohort of elderly women.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
Libero Santarpia ◽  
Takayuki Iwamoto ◽  
Angelo Di Leo ◽  
Naoki Hayashi ◽  
Martha Stampfer ◽  
...  

1012 Background: We aimed to assess the prognostic and predictive role of DNA repair genes in breast cancer (bc) molecular subtypes. Methods: We evaluated Affymetrix gene expression profiling from untreated N- patients (N = 684), neoadjuvant treated tumors with taxanes- (N = 320), anthracyclines- (N = 211), and cisplatin- (N = 22) containing regimens. We assessed within 3 BC molecular subgroups (ER+/HER2-, HER2+, and ER-/HER2-) bimodality distribution, prognosis by association with distant relapse (N = 454, N = 105, and N = 125) and predictive value for likelihood of pathological complete response (pCR) (N = 208, N = 105, and N = 240). Moreover, we explored the function of relevant genes in BC cell lines. Results: Three genes (ERCC2, XRCC3, and RECQL4) showed bimodality in each bc subtype. Eight genes were associated with poor prognosis (including RECQL4) and 1 gene with good prognosis (ATM) [P < .0001] only in ER+/HER2- tumors. Our results suggest a subtype and treatment specific association with pCR although they did not satisfy stringent criteria for false discovery correction. In ER-/HER2- mismatch repair (MR) (MSH2 and MSH6) and MTMR15 genes were associated with response and resistance to taxane-containing regimens, respectively. TOP2A was the only gene associated with response to anthracycline but not taxanes in HER2+ tumors. RECQL4 had a positive trend with higher pCR in both ER+ and ER-/HER2- tumors. In in vitro studies we found that RECQL4 interacts with PARP1 and that the expression of these genes was correlated with sensitivity to chemotherapy and PARP inhibitors. Conclusions: We identified MR genes as potential predictive markers of response to taxanes-based regimens in ER-/HER2-. A novel gene RECQL4 showed bimodal distribution, prognostic value, and a trend for predictive association with response to taxanes-based chemotherapy, which was also confirmed by in vitro analysis. ATM deserves further evaluation as prognostic marker in ER+/HER2-.


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