No Association Between Statin Use and the Prognosis of Endometrial Cancer in Women With Type 2 Diabetes

Preclinical studies have suggested statins have antiproliferative and anti-metastatic effects on endometrial cancer cells. Similarly, most previous epidemiological studies have reported a better prognosis of endometrial cancer in patients who used statins. In this study, we explored the role of statins in the prognosis of endometrial cancer in women with type 2 diabetes in a hospital-based cohort. This retrospective cohort consisted of 119 women with type 2 diabetes who were diagnosed and treated for endometrial cancer at Oulu University Hospital, Finland, between 2007 and 2014. The patients were classified as statin users (n = 58) and nonusers (n = 61) based on the type of medication they were using at the time of endometrial cancer diagnosis. Statin use showed no association with progression-free survival or overall survival in the whole cohort nor the subgroups with type I or type II histology, in lower or higher body mass index groups, or at an early or advanced stage. The results remained similar in the multivariate analysis after adjusting for the patient’s age, cancer stage, and histology. Furthermore, statin use seemed not to have any association with most of the prognostic factors at the time of endometrial cancer diagnosis.

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mSphere of Influence: the Key Role of Neutrophils in Tuberculosis and Type 2 Diabetes Comorbidity

mSphere ◽

10.1128/msphere.00251-21 ◽

2021 ◽

Vol 6 (3) ◽

Author(s):

Anne E. Mayer Bridwell

Keyword(s):

Type 2 Diabetes ◽

Metabolic Regulation ◽

Neutrophil Extracellular Trap ◽

Type I ◽

Pathological Feature ◽

Link Type ◽

Systems Immunology ◽

Shed Light

ABSTRACT Annie Mayer Bridwell works in the field of tuberculosis pathogenesis from the host perspective. She is fascinated by comorbidities, and in this paper, she reflects on three publications that shaped her model of neutrophil-centric pathology in tuberculosis and type 2 diabetes comorbidity. She explains that “Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications” (C. A. Prada-Medina, K. F. Fukutani, N. Pavan Kumar, L. Gil-Santana, et al., Sci Rep 7:1999, 2017, https://doi.org/10.1038/s41598-017-01767-4) led her to consider neutrophils as a central immunological player in comorbid patients. “Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis” (L. Moreira-Teixeira, P. J. Stimpson, E. Stavropoulos, S. Hadebe, et al., Nat Commun 11:5566, 2020, https://doi.org/10.1038/s41467-020-19412-6) and “Diabetes primes neutrophils to undergo NETosis, which impairs wound healing” (S. L. Wong, M. Demers, K. Martinod, M. Gallant, et al., Nat Med 21:815–819, 2015, https://doi.org/10.1038/nm.3887) then shed light on neutrophil extracellular trap (NET) formation as a common pathological feature of dysregulated neutrophils in tuberculosis and diabetes, respectively. Together, these works laid the foundation for Dr. Mayer Bridwell's interest in metabolic regulation of NETosis during TB infection and diabetes comorbidity.

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Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms221910502 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10502

Author(s):

Agostino Milluzzo ◽

Andrea Maugeri ◽

Martina Barchitta ◽

Laura Sciacca ◽

Antonella Agodi

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Vision Loss ◽

Promoter Hypermethylation ◽

Epidemiological Studies ◽

Epigenetic Mechanisms ◽

Diabetes Retinopathy ◽

Modifiable Factors

Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.

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FTO suppresses STAT3 activation and modulates proinflammatory interferon-stimulated gene expression

10.1101/2021.07.23.453596 ◽

2021 ◽

Author(s):

Michael J McFadden ◽

Matthew T. Sacco ◽

Kristen A. Murphy ◽

Moonhee Park ◽

Nandan S. Gokhale ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type I Interferon ◽

Type I ◽

Type I Ifn ◽

Rna Modifications ◽

Inflammatory Genes

Signaling initiated by type I interferon (IFN) results in the induction of hundreds of IFN-stimulated genes (ISGs). The type I IFN response is important for antiviral restriction, but aberrant activation of this response can lead to inflammation and autoimmunity. Regulation of this response is incompletely understood. We previously reported that the mRNA modification m6A and its deposition enzymes, METTL3 and METTL14 (METTL3/14), promote the type I IFN response by directly modifying the mRNA of a subset of ISGs to enhance their translation. Here, we determined the role of the RNA demethylase FTO in the type I IFN response. FTO, which can remove either m6A or the cap-adjacent m6Am RNA modifications, has previously been associated with obesity and body mass index, type 2 diabetes, cardiovascular disease, and inflammation. We found that FTO suppresses the transcription of a distinct set of ISGs, including many known pro-inflammatory genes, and that this regulation is not through the actions of FTO on m6Am. Further, we found that depletion of FTO led to activation of STAT3, a transcription factor that mediates responses to various cytokines, but whose role in the type I IFN response is not well understood. This activation of STAT3 increased the expression of a subset of ISGs. Importantly, this increased ISG induction resulting from FTO depletion was partially ablated by depletion of STAT3. Together, these results reveal that FTO negatively regulates STAT3-mediated signaling that induces proinflammatory ISGs during the IFN response, highlighting an important role for FTO in suppression of inflammatory genes.

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COMPARATIVE HORMONE-ASSOCIATED AND CLINICAL-MORPHOLOGICAL FEATURES OF BREAST AND ENDOMETRIAL CANCER IN PATIENTS WITH AND WITHOUT DIABETES

Problems in oncology ◽

10.37469/0507-3758-2017-63-5-753-758 ◽

2017 ◽

Vol 63 (5) ◽

pp. 753-758

Author(s):

Irina Kovalenko ◽

Lev Bershteyn

Keyword(s):

Breast Cancer ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Endometrial Cancer ◽

Morphological Characteristics ◽

Specific Effect ◽

Antidiabetic Therapy ◽

Course Characteristics

The article presents a comparative analysis of clinical and morphological characteristics of tumor process in patients with breast cancer and endometrial cancer with diabetes mellitus and without it. Previously little-known features of the tumor process in combination with diabetes were revealed. The data obtained indicated that in case of breast cancer the presence of diabetes for a number of signs influenced the course/characteristics of the disease: e.g., the tumor size was significantly greater than in patients without diabetes and highly differentiated Gltumors were less common. In case of endometrial cancer, diabetes (but only in combination with obesity or postmenopausal period) was combined with more favorable characteristics of tumor indicating a diagnosis-specific effect of Type 2 diabetes in regard of the tumor process features. An evaluation of the role of antidiabetic therapy variant discovered that in patients with breast cancer metformin therapy was combined with more frequent detection of highly differentiated, hormone-positive tumors, which was not revealed in patients with endometrial cancer.

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