scholarly journals The use of metformin in the treatment of gastrointestinal cancer

2021 ◽  
pp. 60-69
Author(s):  
S. M. Tkach
Keyword(s):  
Diabetes Mellitus ◽  
Cancer Progression ◽  
Gastrointestinal Cancer ◽  
Low Cost ◽  
Epidemiological Studies ◽  
Systemic Effect ◽  
Disease Stage ◽  
Antitumor Effects ◽  
Incidence And Mortality ◽  
Patients With Diabetes

Type 2 diabetes mellitus and malignancies have several common risk factors, such as obesity, metabolic syndrome, hyperinsulinemia, and chronic inflammation. Currently these factors are considered as possible mechanisms that increase the risk of the development of malignanttumors, including gastrointestinal cancer. Epidemiological studies and meta-analyses indicate that patients with diabetes have a higher incidence and mortality from malignancies. Metformin is well-known oral hypoglycemic drug that belongs to the biguanide class and is being used to treat diabetes mellitus for almost a century. It has been established that in patients with diabetes mellitus, long-term use of metformin reduces the incidence of tumors and mortality from various cancers. The results of recent studies suggest that metformin may have direct pleiotropic anticancer activity against many tumor cells and their microenvironment. Its potential mechanisms include both insulin-dependent and insulin-independent. Moreover, metformin promotes antitumor immunosuppressive metabolic control of T lymphocytes and cancer cells, it is able to modulate the intestinal microbiota and renders a systemic effect on a body metabolism. The article presents data that reveal possible mechanisms of anticancer action of metformin and justify the use of metformin as a drug that may be useful for the treatment of gastrointestinal cancer. Although most of the clinical trials have retrospective design, they are often limited in time and patient bias, recent data from preclinical studies on the antitumor effects of metformin suggest that its effects on carcinogenesis and gastrointestinal cancer progression need to be further investigated. Future studies should consider the diabetic status, prognostic biomarkers, disease stage, and treatment regimens. Given that metformin is a safe and widely available drug with low cost, the feasibility of further study of its anti-cancer effects is beyond doubt.

scholarly journals Screening Strategy of Pancreatic Cancer in Patients with Diabetes Mellitus

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 572
Author(s):  
Suguru Mizuno ◽  
Yousuke Nakai ◽  
Kazunaga Ishigaki ◽  
Kei Saito ◽  
Hiroki Oyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Cancer ◽  
Epidemiological Studies ◽  
Screening Strategy ◽  
Diabetic Patients ◽  
Reverse Causality ◽  
Pilot Studies ◽  
Patients With Diabetes ◽  
High Risk Populations ◽  
New Onset

The incidence of pancreatic cancer (PCa) is increasing worldwide and has become one of the leading causes of cancer-related death. Screening for high risk populations is fundamental to overcome this intractable malignancy. Diabetes mellitus (DM) is classically known as a risk factor for PCa. Recently the reverse causality is in the spotlight, that is to say, DM is considered to be a manifestation of PCa. Numbers of epidemiological studies clarified that new-onset DM (≤2-year duration) was predominant in PCa patients and the relative risk for PCa inversely correlated with duration of DM. Among patients with new-onset DM, elder onset, weight loss, and rapid exacerbation of glycemic control were reported to be promising risk factors and signs, and the model was developed by combining these factors. Several pilot studies disclosed the possible utility of biomarkers to discriminate PCa-associated DM from type 2 DM. However, there is no reliable biomarkers to be used in the practice. We previously reported the application of a multivariate index for PCa based on the profile of plasma free amino acids (PFAAs) among diabetic patients. We are further investigating on the PFAA profile of PCa-associated DM, and it can be useful for developing the novel biomarker in the near future.

scholarly journals PERBANDINGAN MOTIVASI PENGGUNAAN MODERN DRESSING PADA PENDERITA ULKUS DIABEKTIKUM DI KELURAHAN KALIJIRAK DAN KELURAHAN WONOLOP O KECAMATAN TASIKMADU KARANGANYAR

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Budi Kristanto ◽  
Nur Cahyo Saputro ◽  
Elga Firdian Candra
Keyword(s):  
Diabetes Mellitus ◽  
Study Design ◽  
Analytical Study ◽  
Diabetes Complications ◽  
Wound Care ◽  
Epidemiological Studies ◽  
Diabetic Ulcers ◽  
The World ◽  
Patients With Diabetes ◽  
The Village

ABSTRACTIntroduction: The increasing prevalence of diabetes in the world led to an increase in cases of amputation due to diabetes complications. Epidemiological studies reported more than one million amputations are performed on people with diabetes each year. Therefore, prevention and appropriate management of lesions of the foot is the most important thing. The development of wound care is growing very rapidly in the world of health.Objective: This study aimed to compare the motivation of the use of modern dressings in patients with diabetic ulcers in the Wonolopo and Kalijirak villagedistrict of Karanganyar.Methods: This study is a comparative analytical study design to compare the motivation of the use of modern dressings in patients with diabetic ulcers in the Wonolopo and Kalijirak village district of Karanganyar.Respondents: The study sample was taken from the population of people who have diabetic ulcers in the Village Kalijirak as much as 20 and as many as 20 Wonolopo village.Results: Based on the results of independent sample t test with SPSS for Windows series 18 with α = 5% (0.05), obtained p equal to 0825 which means p> 0.05 it indicates that Ha is not accepted, which means there is no difference in motivation to use modern dressings in patients with diabetes mellitus with diabetic ulcers among respondents in the Village and Village Wonolopo Kalijirak.Keywords: Motivation, Modern dressings, Wound care

scholarly journals Diabetes mellitus and periodontal diseases: A two way relationship

2021 ◽  
Vol 6 (2) ◽  
pp. 43-56
Author(s):  
Gowhar Nazir ◽  
◽  
Josee Amin ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Periodontal Disease ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Systemic Effect ◽  
Diabetic Patients ◽  
Periodontal Infection ◽  
Bidirectional Relationship ◽  
Patients With Diabetes ◽  
Global Health Care

Diabetes mellitus and periodontits are both highly prevalent chronic inflammatory diseases. Both diseases share the same risk factors and are a significant global health care burden adversely affecting the quality of life. Evidence from various studies have demonstrated that diabetes is a major risk factor for periodontal disease and is associated with increased incidence, prevalence and severity of periodontal disease. Hyperglycemia associated with diabetes mellitus results in an increased host immunoinflammatory response which adversely affects the periodontal health. Conversely, periodontits is associated with poor metabolic control in patients with diabetes and increased development of diabetic complications suggesting a bidirectional relationship between the two diseases. Periodontal infection via bacteremia exerts a wide systemic effect by contributing to chronic systemic inflammatory burden worsening diabetic state by increasing insulin resistance. Moreover, studies have demonstrated an improvement in glycemic control following periodontal therapy in prediabetic and diabetic patients with periodontitis.

scholarly journals Novel Metformin Analogues for Treatment of Pancreatic Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1027-A1028
Author(s):  
Lorena P Burton ◽  
Gang Deng ◽  
Cristian D Yanes ◽  
Jaydutt V Vadgama ◽  
Michael E Jung ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Progression ◽  
Clinical Benefit ◽  
Diabetes Mellitus Type 2 ◽  
Mtor Signaling ◽  
Diabetes Mellitus Type ◽  
Antitumor Effects ◽  
Incidence And Mortality

Abstract Pancreatic ductal adenocarcinoma (PDCA) is a leading cause of cancer death in the US. Patients diagnosed with PDCA generally present with advanced disease with poor prognosis and limited treatment options. African American patients have higher incidence and mortality of PDCA than Caucasian American or any other ethnic group. Different factors have been attributed to contribute to this health disparity, among them higher incidence of Diabetes Mellitus type 2. To address the need for new therapeutic approaches, we note epidemiologic reports that patients with diabetes mellitus-type 2 treated with the biguanide drug metformin, but not other antidiabetic drugs, have a reduced risk of PDCA and an increased survival rate among those with PDCA. The main physiologic effect of metformin is to lower blood glucose and reduce hyperinsulinemia associated with insulin resistance. In the cell, metformin stimulates AMP-activated protein kinase (AMPK) that in turn inhibits mTORC1 which integrates signals from an array of intracellular pathways to regulate cell growth. Recent clinical trials describe modest antiproliferative effects from use of neoadjuvant metformin, but no significant clinical benefit occurred when metformin was dosed at glycemic control levels in patients with advanced cancers. These findings suggest that development of more potent anticancer analogues of metformin may help to boost clinical benefit and patient survival. Hence, we have designed new biguanide analogues of metformin, and screening of these compounds in preclinical PDCA models show that selected analogues are more efficacious in blocking tumor progression than parental metformin at lower doses. Using proliferation assays in vitro, PDCA cells (Panc 1, MIA Paca-2) were treated 72-hrs with metformin or analogues, and greater dose-dependent inhibition of PDCA cell proliferation was found with analogues as compared to metformin (P<0.001). Further, apoptosis was also markedly induced by metformin analogues as compared to parental metformin (P<0.01). Antitumor effects of metformin are attributed in part to activation LKB1-AMPK pathways and downstream blockade of mTOR signaling, which is often increased in PDCA cells. Using PDCA cells treated in vitro with analogues for 24-hrs, we find that analogues induce AMPK phosphorylation and suppression of mTOR signaling, thus blocking protein synthesis and tumor proliferation. With an in vivo PANC 1 xenograft model in nude mice, lead metformin analogues given by oral gavage daily significantly inhibited tumor progression over 28-days as compared to appropriate controls (P<0.0001). Our findings show that selected metformin analogues have potent anticancer activity in preclinical PDCA models and may have promise as new targeted therapeutics for patients afflicted with this deadly disease. [Funded by NIH/NCI R21CA176337 and NIH/NCI U54 CA143930]

scholarly journals Wearable Sensor for Assessing Gait and Postural Alterations in Patients with Diabetes: A Scoping Review

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1145
Author(s):  
Lorenzo Brognara ◽  
Antonio Mazzotti ◽  
Alberto Di Martino ◽  
Cesare Faldini ◽  
Omar Cauli
Keyword(s):  
Diabetes Mellitus ◽  
Low Cost ◽  
Public Health Problem ◽  
Gait Velocity ◽  
Diabetic Patients ◽  
Wearable Sensor ◽  
Posture Analysis ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Spatiotemporal Parameters

Background and Objectives: Diabetes mellitus is considered a serious public health problem due to its high prevalence and related complications, including gait and posture impairments due to neuropathy and vascular alterations and the subsequent increased risk of falls. The gait of patients with diabetes is characterized by alterations of the main spatiotemporal gait parameters such as gait velocity, cadence, stride time and length, which are also known to worsen with disease course. Wearable sensor systems can be used for gait analysis by providing spatiotemporal parameters and postural control (evaluated from the perspective of body sway), useful for investigating the disease progression. Thanks to their small size and low cost of their components, inertial measurement units (IMUs) are easy to wear and are cheap tools for movement analysis. Materials and Methods: The aim of this study is to review articles published in the last 21 years (from 2000 to 2021) concerning the application of wearable sensors to assess spatiotemporal parameters of gait and body postural alterations in patients with diabetes mellitus. Relevant articles were searched in the Medline database using PubMed, Ovid and Cochrane libraries. Results: One hundred and four articles were initially identified while searching the scientific literature on this topic. Thirteen were selected and analysed in this review. Wearable motion sensors are useful, noninvasive, low-cost, and objective tools for performing gait and posture analysis in diabetic patients. The IMUs can be worn at the lumber levels, tibias or feet, and different spatiotemporal parameters of movement and static posture can be assessed. Conclusions: Future research should focus on standardizing the measurement setup and selecting the most informative spatiotemporal parameters for gait and posture analysis.

Obesity in the Elderly — On the Role of Adipokines in Prostate Cancer Progression

2012 ◽  
Vol 08 (01) ◽  
pp. 46
Author(s):  
Adriano Angelucci ◽  
Mauro Bologna ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Preventive Strategy ◽  
Age Related ◽  
Incidence And Mortality ◽  
Frequent Site

The prostate is the most frequent site of cancer in men aged 68 years and older. Although prostate cancer is frequently a slow-progressing cancer, the increase in lifespan is posing new challenges in order to avoid prostate cancer-associated mortality. Epidemiological studies have clearly demonstrated that the westernised lifestyle and diet may fuel prostate cancer incidence and mortality, and the associated current pandemic of obesity is becoming one of the principal risk factors for age-related chronic diseases. Obesity and ageing seem to contribute independently to deregulating adipose tissue homoeostasis and in turn systemic metabolism. Nowadays, adipose tissue is recognised as an active and complex endocrine and immunological organ able to control the homoeostasis of different distant organs through the release of a variety of factors, collectively termed adipokines. These factors are master regulators of energy balance and immune response and may account for some of the most frequent obesity- and age-related health problems, including cancer. The dissection of mechanisms leading to altered metabolic control by adipose tissue will eventually indicate a new preventive strategy for prostate cancer.

scholarly journals Effects and Mechanisms of Tea for the Prevention and Management of Diabetes Mellitus and Diabetic Complications: An Updated Review

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 170 ◽  
Author(s):  
Jin-Ming Meng ◽  
Shi-Yu Cao ◽  
Xin-Lin Wei ◽  
Ren-You Gan ◽  
Yuan-Feng Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Mechanisms Of Action ◽  
Health Concern ◽  
High Morbidity ◽  
Protective Effects ◽  
Public Health Concern ◽  
Β Cells ◽  
Patients With Diabetes

Diabetes mellitus has become a serious and growing public health concern. It has high morbidity and mortality because of its complications, such as diabetic nephropathy, diabetic cardiovascular complication, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy. Epidemiological studies revealed that the consumption of tea was inversely associated with the risk of diabetes mellitus and its complications. Experimental studies demonstrated that tea had protective effects against diabetes mellitus and its complications via several possible mechanisms, including enhancing insulin action, ameliorating insulin resistance, activating insulin signaling pathway, protecting islet β-cells, scavenging free radicals, and decreasing inflammation. Moreover, clinical trials also confirmed that tea intervention is effective in patients with diabetes mellitus and its complications. Therefore, in order to highlight the importance of tea in the prevention and management of diabetes mellitus and its complications, this article summarizes and discusses the effects of tea against diabetes mellitus and its complications based on the findings from epidemiological, experimental, and clinical studies, with the special attention paid to the mechanisms of action.

scholarly journals Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response

2020 ◽  
Vol 6 (40) ◽  
pp. eaba5714 ◽  
Author(s):  
Yaron Vinik ◽  
Francisco Gabriel Ortega ◽  
Gordon B. Mills ◽  
Yilling Lu ◽  
Menucha Jurkowicz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Proteomic Analysis ◽  
Low Cost ◽  
Disease Stage ◽  
Therapeutic Monitoring ◽  
Healthy Controls ◽  
Proteomic Profiling ◽  
Risk Of Cancer

Proteomic profiling of circulating small extracellular vesicles (sEVs) represents a promising, noninvasive approach for early detection and therapeutic monitoring of breast cancer (BC). We describe a relatively low-cost, fast, and reliable method to isolate sEVs from plasma of BC patients and analyze their protein content by semiquantitative proteomics. sEV-enriched fractions were isolated from plasma of healthy controls and BC patients at different disease stages before and after surgery. Proteomic analysis of sEV-enriched fractions using reverse phase protein array revealed a signature of seven proteins that differentiated BC patients from healthy individuals, of which FAK and fibronectin displayed high diagnostic accuracy. The size of sEVs was significantly reduced in advanced disease stage, concomitant with a stage-specific protein signature. Furthermore, we observed protein-based distinct clusters of healthy controls, chemotherapy-treated and untreated postsurgery samples, as well as a predictor of high risk of cancer relapse, suggesting that the applied methods warrant development for advanced diagnostics.

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