Carotid artery occlusion and colateral circulation in C57black/6J mice detected by synchrotron radiation microangiography

Using monochromatic synchrotron radiation, we performed microangiography inC57BL/6J mice and investigated their vasculature after unilateral and bilateral carotidartery occlusion. Bilateral occlusion of the carotid artery was made by a ligation of theleft common carotid artery followed by a ligation of the right internal carotid artery(ICA) two days later (n=12). Five days after the second surgery, angiography wasperformed. Unilateral occlusion was made by clipping the right ICA and thenangiography was performed immediately (n=5). The control mice did not undergo anyocclusion (n=5). We removed the brain of the bilateral occlusion mice afterangiography and examined the infarction area. The cerebral microvessels in all animalswere clearly visualized. In the control mice, the posterior communicating artery (Pcom)was not visualized. In the unilateral occlusion mice, the anastomosis of thepterygopalatine artery (PPA) and the external carotid artery (ECA) were recognized.The PPA is thus considered to play a role in the collateral vessel between the ICA andthe ECA. The Pcom was not visualized. In the bilateral occlusion mice, the Pcom wasobserved either unilateraly (n=5) or bilateraly (n=5). The Pcom supplied blood flow tothe anterior circulation from the vertebrobasilar arteries. The bilateral occlusion micethat had at least one visualized Pcom did not have any infarction. We could successfullyvisualize the cerebral vasculature of normal mice and carotid artery occluded mice inan in vivo study. Microangiography can demonstrate the development of vasculatureand the blood flow dynamics in mice

Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

[Background]Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. [Methods]We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. [Results]NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33–3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21–3.93) were associated with disease-free survival in NBNC HCC patients. [Conclusions]The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients

Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis

Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO-Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO-Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.FCT: (SFRH/BPD/74313/2010), Calouste Gulbenkian Foundation

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

ジュウニシチョウ ブルンナーセン カケイセイ ニ オコル イ ネンマク カセイ ノ イケイ ニ ツイテ : ブルンナーセン ガン ノ ゼンク ビョウヘン ニ カンスル ケンキュウ

京都大学0048新制・論文博士博士(医学)乙第11814号論医博第1897号新制||医||927(附属図書館)24356UT51-2006-J511(主査)教授 千葉 勉, 教授 武藤 誠, 教授 横出 正之学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA