Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life

Modesitt, Susan C.; Hallowell, Peter T.; Slack‐Davis, Jill K.; Michalek, Ryan D.; Atkins, Kristen A.; Kelley, Sarah; Arapovic, Sanja; Shupnik, Margaret A.; Hoehn, Kyle L.

doi:10.1016/j.ygyno.2015.05.015

Cited by 63 publications

(50 citation statements)

References 26 publications

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“…In the context of what is known, several comments can be made. Previous studies found rates and severity of endometrial pathology lower than ours, probably because in these other studies, progestin therapy was frequent, women with abnormal bleeding were excluded and failed or inadequate biopsies were common. Our participants were more obese and insulin resistant than women in previously reported cohorts, which may be causally important .…”

Section: Discussioncontrasting

confidence: 84%

“…25,26 Elevated circulating insulin and insulin-like growth factor (IGF)-I are thought to drive endometrial proliferation through PI3K-AKT-mTOR pathway activation. 9 In our study, bariatric surgery precipitated changes in systemic metabolic parameters, inflammatory markers and reproductive hormone profiles, which mirrored published work, 21,27,28 however the role of these systemic changes in mediating tissue effects remains unclear.…”

Section: Strengths and Limitationssupporting

confidence: 86%

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The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

MacKintosh

Derbyshire

McVey

et al. 2018

Intl Journal of Cancer

102

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Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery‐induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III–IV obesity (body mass index ≥40 and ≥50 kg/m 2 , respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months’ follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki‐67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy‐two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was −32.7 and −62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki‐67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA‐IR) and inflammation (hsCRP, IL‐6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down‐regulation of PI3K‐AKT–mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.

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Section: Discussioncontrasting

confidence: 84%

Section: Strengths and Limitationssupporting

confidence: 86%

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

MacKintosh

Derbyshire

McVey

et al. 2018

Intl Journal of Cancer

102

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“…Metabolomics analyses were performed by Metabolon, Inc. (Durham, North Carolina, USA) as previously described4243 from 30 mg frozen liver tissue. Samples were stored at −80 °C until processed.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival

et al. 2017

Self Cite

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The metabolic pathway of de novo lipogenesis is frequently upregulated in human liver tumours, and its upregulation is associated with poor prognosis. Blocking lipogenesis in cultured liver cancer cells is sufficient to decrease cell viability; however, it is not known whether blocking lipogenesis in vivo can prevent liver tumorigenesis. Herein, we inhibit hepatic lipogenesis in mice by liver-specific knockout of acetyl-CoA carboxylase (ACC) genes and treat the mice with the hepatocellular carcinogen diethylnitrosamine (DEN). Unexpectedly, mice lacking hepatic lipogenesis have a twofold increase in tumour incidence and multiplicity compared to controls. Metabolomics analysis of ACC-deficient liver identifies a marked increase in antioxidants including NADPH and reduced glutathione. Importantly, supplementing primary wild-type hepatocytes with glutathione precursors improves cell survival following DEN treatment to a level indistinguishable from ACC-deficient primary hepatocytes. This study shows that lipogenesis is dispensable for liver tumorigenesis in mice treated with DEN, and identifies an important role for ACC enzymes in redox regulation and cell survival.

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“…WTT only checks whether the two populations have equal means [46]. WTT is widely used in various applications to select important features [47][48][49]. The WTT is computed by:…”

Section: Feature Selectionmentioning

confidence: 99%

Pathological Brain Detection by a Novel Image Feature—Fractional Fourier Entropy

Wang

Zhang

Yang

et al. 2015

Entropy

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Aim: To detect pathological brain conditions early is a core procedure for patients so as to have enough time for treatment. Traditional manual detection is either cumbersome, or expensive, or time-consuming. We aim to offer a system that can automatically identify pathological brain images in this paper. Method: We propose a novel image feature, viz., Fractional Fourier Entropy (FRFE), which is based on the combination of Fractional Fourier Transform (FRFT) and Shannon entropy. Afterwards, the Welch's t-test (WTT) and Mahalanobis distance (MD) were harnessed to select distinguishing features. Finally, we introduced an advanced classifier: twin support vector machine (TSVM). Results: A 10ˆK-fold stratified cross validation test showed that this proposed "FRFE + WTT + TSVM" yielded an accuracy of 100.00%, 100.00%, and 99.57% on datasets that contained 66, 160, and 255 brain images, respectively. Conclusions: The proposed "FRFE + WTT + TSVM" method is superior to 20 state-of-the-art methods.

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Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life

Cited by 63 publications

References 26 publications

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival

Pathological Brain Detection by a Novel Image Feature—Fractional Fourier Entropy

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