Uterine Fibroid Embolization

Uterine fibroids or leiomyomas are benign, hormone-dependent smooth muscle cell tumors that can be associated with menorrhagia, anemia, pelvic pain, urinary and/or intestinal symptoms, and dyspareunia. Traditionally, the mainstay of treatment has been surgical, consisting of hysterectomy or myomectomy. However, uterine artery embolization has become an increasingly utilized, minimally invasive treatment modality that can be offered as either sole therapy or as a staged, pre-operative measure to hysterectomy. A thorough knowledge of pelvic vascular anatomy and facility with specific embolotherapeutic techniques are required for safe and effective fibroid embolization

The miR-17∼92 microRNA cluster Is a global regulator of tumor metabolism

SummaryA central hallmark of cancer cells is the reprogramming of cellular metabolism to meet the bioenergetic and biosynthetic demands of malignant growth. Here, we report that the miR-17∼92 microRNA (miRNA) cluster is an oncogenic driver of tumor metabolic reprogramming. Loss of miR-17∼92 in Myc+ tumor cells leads to a global decrease in tumor cell metabolism, affecting both glycolytic and mitochondrial metabolism, whereas increased miR-17∼92 expression is sufficient to drive increased nutrient usage by tumor cells. We mapped the metabolic control element of miR-17∼92 to the miR-17 seed family, which influences cellular metabolism and mammalian target of rapamycin complex 1 (mTORC1) signaling through negative regulation of the LKB1 tumor suppressor. miR-17-dependent tuning of LKB1 levels regulates both the metabolic potential of Myc+ lymphomas and tumor growth in vivo. Our results establish metabolic reprogramming as a central function of the oncogenic miR-17∼92 miRNA cluster that drives the progression of MYC-dependent tumors

The LKB1-AMPK axis governs metabolic reprograming and tumour progression in lymphoma

Over the course of transformation, the cancer cell must adapt its metabolism in support of proliferation. A common feature among cancer cells is the engagement of the Warburg effect, a tendency toward glycolysis and lactic acid production despite adequate oxygenation. The molecular events that occur during metabolic reprograming in cancer remain to be defined. AMP activated protein kinase (AMPK) is a cellular energetics sensor that governs the balance between anabolic and catabolic metabolism based on environmental and cellular signals. The upstream kinase of AMPK, liver kinase B1 (LKB1) is an established tumour suppressor and metabolic regulator, yet the role of AMPK in cancer is not clear. Herein, we describe a tumour suppressive and metabolic regulatory function of AMPK in cancer. Using a Myc model of B cell lymphoma, we find that AMPK deletion accelerates tumourigenesis and promotes the Warburg effect. The polycistronic, oncogenic microRNA cluster miR-17~92 is transcriptionally activated by Myc, and we find that miR-17~92 acts as a negative regulator of the LKB1-AMPK axis downstream of Myc to engage metabolic reprograming. We describe how the miR-17 family inhibits the translation of LKB1, which consequently sensitizes cells to metabolic stress. We employ biguanides, which act as complex I inhibitors, and show that those cells overexpressing miR-17~92 are especially sensitive to treatment. Our work provides evidence for the tumour suppressive capacity of AMPK, and describes a Myc-miR-17~92-LKB1 regulatory circuit that orchestrates metabolic reprograming in cancer.Au cours de sa transformation, la cellule cancéreuse doit adapter son métabolisme pour proliférer. Une caractéristique commune parmi les cellules cancéreuses est l'engagement de l'effet Warburg, une tendance vers la production de glycolyse et d'acide lactique malgré l'oxygénation adéquate. Les évènements moléculaires qui se produisent lors de la reprogrammation dans le cancer restent à définir. AMP activated protein kinase (AMPK) est un détecteur de santé énergétique qui régit l'équilibre entre le métabolisme anabolique et catabolique basé sur les signaux environnementaux et cellulaires. Le maître kinase d'AMPK, liver kinase B1 (LKB1) est un suppresseur de tumeur ainsi qu'un régulateur de métabolisme établi. Ici, nous décrivons une fonction de suppression tumorale et métabolique de l'AMPK dans le cancer. À l'aide d'un modèle Myc de lymphome diffus à grandes cellules B, nous trouvons que l'inactivation de l'AMPK accélère la tumorigénèse et favorise l'effet Warburg. Le micro-ARN polycistronique et oncogène, miR-17~92, est activé transcriptionellement par Myc et nous trouvons que miR-17~92 agit comme un régulateur négatif de l'axe LKB1-AMPK pour engager la reprogrammation métabolique. Nous décrivons la manière dont la famille miR-17 inhibe la traduction de LKB1, ce qui sensibilise les cellules au stress métabolique. Nous employons des biguanides qui agissent comme des inhibiteurs complexes I et démontrons que ces cellules surexprimant miR-17~92 sont particulièrement sensibles au traitement. Notre travail fournit preuve de la capacité d'AMPK comme suppresseur de tumeur et décrit un circuit régulateur Myc-miR-17~92-LKB1 qui dirige la reprogrammation métabolique dans le cancer

Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α

One of the major metabolic changes associated with cellular transformation is enhanced nutrient utilization, which supports tumor progression by fueling both energy production and providing biosynthetic intermediates for growth. The liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor that couples bioenergetics to cell-growth control through regulation of mammalian target of rapamycin (mTOR) activity; however, the influence of LKB1 on tumor metabolism is not well defined. Here, we show that loss of LKB1 induces a progrowth metabolic program in proliferating cells. Cells lacking LKB1 display increased glucose and glutamine uptake and utilization, which support both cellular ATP levels and increased macromolecular biosynthesis. This LKB1-dependent reprogramming of cell metabolism is dependent on the hypoxia-inducible factor-1α (HIF-1α), which accumulates under normoxia in LKB1-deficient cells and is antagonized by inhibition of mTOR complex I signaling. Silencing HIF-1α reverses the metabolic advantages conferred by reduced LKB1 signaling and impairs the growth and survival of LKB1-deficient tumor cells under low-nutrient conditions. Together, our data implicate the tumor suppressor LKB1 as a central regulator of tumor metabolism and growth control through the regulation of HIF-1α–dependent metabolic reprogramming