Metformin is an AMP Kinase-Dependent Growth Inhibitor for Breast Cancer Cells

Abstract

A new approach to treating urodynamic stress incontinence (USI) is the transobturator tension-free vaginal tape (TOT). Inserting a suburethral tape at the mid-urethral level by the perineal route provides a minimally invasive means of reinforcing the structures that support the urethra. This approach, first described as the tension-free vaginal tape procedure, makes it unnecessary to gain blind entry into the retropubic space with the attendant risks of injuring the bladder, bowel, major blood vessels, or nerves.This retrospective cohort study was planned to determine the frequency of-and risk factors for-lower urinary tract (LUT) injuries in 389 women who, in the years 2002-2006, had a TOT procedure as treatment for USI at a tertiary referral urogynecology center. The outside-in technique was used in 241 cases, most often with Obtape®, while the remaining 148 women were operated on using the inside-out technique. In 70% of cases, the TOT procedure was primary surgery for USI. In 111 cases, another surgical procedure was carried out at the same time.Four LUT injuries were documented, 2 affecting the urethra and 2 the bladder. All 4 women had surgery using the outside-in technique, but this was not a statistically significant finding. Three of the 4 women with injuries underwent another procedure involving colporrhaphy. Both women with urethral injury underwent TOT surgery as a secondary procedure. In contrast, both those with bladder injuries were undergoing primary continence surgery. The overall incidence of LUT injury in this series was 1%.LUT injury is an infrequent complication of TOT procedures. In the present series of nearly 400 women, LUT injuries occurred only when using the outside-in technique. Intraoperative cystoscopy should be considered in selected cases only, but postoperative problems such as hematuria call for immediate cystoscopy. GYNECOLOGY Volume 62, Number 3 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTThe inability of colposcopy to reliably rule out cervical intraepithelial neoplasia (CIN) 2 or more advanced changes has complicated the management of women diagnosed colposcopically as having human papillomavirus (HPV) or CIN 1. This study assessed the risk of CIN 3 or cancer in a group of women given a colposcopic diagnosis of CIN 1 or less. The participants, with no past history of CIN, underwent colposcopy to evaluate abnormal cervical cytology in the form of atypical Office Gynecology 173 174 Obstetrical and Gynecological Survey Office Gynecology 175 176 Obstetrical and Gynecological Survey ABSTRACTMore than 10% of epithelial ovarian neoplasms are borderline ovarian tumors (BOTS), also known as ovarian tumors of low malignant potential. About one-fourth of them are found in potentially fertile women. Once thought to be a precursor of epithelial ovarian cancer, the BOT now is viewed as a biologically distinct entity. Five-year survival rates exceeding 95% are reported. Among 101 women operated on for BOT in the years 1992-2001 were 22 who had a fertility-preserving procedure in which at l...

Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial

“…AMPK is involved in regulating energy balance at the cellular and whole body levels [6,7] and is activated by stresses that deplete ATP, including glucose deprivation [8,9] and hypoxia. Activation of the AMPK pathway by metformin in breast cancer cell lines reduces cellular proliferation, and is associated with reduced activation of mTOR and S6 kinase [10]. AMPK activation may be down-regulated in untreated primary breast cancer [11] suggesting reactivation of the AMPK pathway may inhibit tumours, sparing normal tissues which already have an active AMPK pathway.…”

Does diabetes therapy influence the risk of cancer?

“…The antitumour effect of metformin seems to be mediated via its ability to increase the AMP-activated protein kinase (AMPK) signalling pathway [11]. AMPK, which is activated by a rise in the AMP:ATP ratio, plays a key role in cellular energy balance.…”

“Overcoming breast cancer drug resistance with mTOR inhibitors”. Could it be a myth or a real possibility in the short-term future?

“…They were down-regulated processes that consume energy, such as protein translation and cell division, and they were up-regulated those that generate energy. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation, suggesting potential roles for activators of AMP kinase such as metformin in cancer prevention and treatment [29]. A more recent study on MCF-7 cells shows that metformin inhibits the initiation step in translation via mTOR and that metformin requires two major tumour suppressors, LKB1 and TSC2, to mediate its effects on translation.…”