77 research outputs found
Disruption of Intraflagellar Transport in Adult Mice Leads to Obesity and Slow-Onset Cystic Kidney Disease
SummaryThe assembly of primary cilia is dependant on intraflagellar transport (IFT), which mediates the bidirectional movement of proteins between the base and tip of the cilium. In mice, congenic mutations disrupting genes required for IFT (e.g., Tg737 or the IFT kinesin Kif3a) are embryonic lethal, whereas kidney-specific disruption of IFT results in severe, rapidly progressing cystic pathology [1–3]. Although the function of primary cilia in most tissues is unknown, in the kidney they are mechanosenstive organelles that detect fluid flow through the tubule lumen [4]. The loss of this flow-induced signaling pathway is thought to be a major contributing factor to cyst formation [5–7]. Recent data also suggest that there is a connection between ciliary dysfunction and obesity as evidenced by the discovery that proteins associated with human obesity syndromes such as Alström and Bardet-Biedl localize to this organelle [8]. To more directly assess the importance of cilia in postnatal life, we utilized conditional alleles of two ciliogenic genes (Tg737 and Kif3a) to systemically induce cilia loss in adults. Surprisingly, the cystic kidney pathology in these mutants is dependent on the time at which cilia loss was induced, suggesting that cyst formation is not simply caused by impaired mechanosensation. In addition to the cystic pathology, the conditional cilia mutant mice become obese, are hyperphagic, and have elevated levels of serum insulin, glucose, and leptin. We further defined where in the body cilia are required for normal energy homeostasis by disrupting cilia on neurons throughout the central nervous system and on pro-opiomelanocortin-expressing cells in the hypothalamus, both of which resulted in obesity. These data establish that neuronal cilia function in a pathway regulating satiety responses
Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study
This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC
Endometrial cancer
Endometrial cancer is the most common gynecological
malignancy in well-developed countries.
Biologically and clinicopathologically,
endometrial carcinomas are divided into two
types: type 1 or estrogen-dependent carcinomas
and type 2 or estrogen-independent carcinomas.
Type 1 cancers correspond mainly to endometrioid
carcinomas and account for approximately
90 % of endometrial cancers, whereas
type 2 cancers correspond to the majority of the
other histopathological subtypes.
The vast majority of endometrial cancers
present as abnormal vaginal bleedings in
postmenopausal women. Therefore, 75 % of
cancers are diagnosed at an early stage, which
makes the overall prognosis favorable.
The first diagnostic step to evaluate women
with an abnormal vaginal bleeding is the measurement
of the endometrial thickness with
transvaginal ultrasound. If endometrial thickening
or heterogeneity is confirmed, a biopsy
should be performed to establish a definite
histopathological diagnosis.
Magnetic resonance imaging is not considered
in the International Federation of Gynaecology
and Obstetrics staging system. Nonetheless it
plays a relevant role in the preoperative staging of
endometrial carcinoma, helping to define the best
therapeutic management. Moreover, it is important
in the diagnosis of treatment complications,
in the surveillance of therapy response, and in the
assessment of recurrent disease.info:eu-repo/semantics/publishedVersio
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