Experimental Evaluation of Mechanical Reliability of the Impeller Blade for Large Integrally Geared Compressors

Lectur

Ovarian clear cell carcinoma meets metabolism; HNF-1β confers survival benefits through the Warburg effect and ROS reduction.

Ovarian clear cell carcinoma (OCCC) constitutes one of the subtypes of ovarian cancers, but it has unique clinical, histological and biological characteristics, one of which is chemo-resistance. It is also known to develop from endometriotic cyst, a benign ovarian tumor, at relatively high frequency. Recently, it is becoming well known that most of OCCCs express HNF1β, a transcription factor, which is closely associated with the development of liver, pancreas and kidney, as well as occurrence of familial forms of type 2 diabetes. Expression of HNF1β is now regarded as a hallmark of this tumor. Nevertheless, exact biological function of this gene in OCCC has not been clarified. We have shown in previous studies that microenvironment in endometriotic cysts contains severe oxidative stress and OCCC develops under such stressful environment as stress-resistant tumor, which may lead to chemo-resistance. We also showed that increased expression of HNF1β facilitates glucose uptake and glycolysis, which is known as Warburg effect. In the previous issue of this journal, by using comprehensive metabolome analysis, we report that HNF1β actually reduces and protects themselves from internal oxidative stress by dramatically changing cellular metabolism. In this article, we review the relevance and significance of cancer-specific metabolism and how they are associated with biological characteristics of OCCC via expression of HNF1β, along with future clinical implications of targeting cancer-specific metabolism

The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients.

Objective: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. Methods: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. Results: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. Conclusion: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model

Experimental Evaluation of Mechanical Reliability of the Impeller Blade for Large Integrally Geared Compressors

Lectur

PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (CCC) exhibits an association with endometriosis, resistance to oxidative stress, and poor prognosis owing to its resistance to conventional platinum-based chemotherapy. A greater understanding of the molecular characteristics and pathogenesis of ovarian cancer subtypes may facilitate the development of targeted therapeutic strategies, though the mechanism of drug resistance in ovarian CCC has yet to be determined. In this study, we assessed exome sequencing data to identify new therapeutic targets of mitochondrial function in ovarian CCC because of the central role of mitochondria in redox homeostasis. Copy number analyses revealed that chromosome 17q21-24 (chr.17q21-24) amplification was associated with recurrence in ovarian CCC. Cell viability assays identified an association between cisplatin resistance and chr.17q21-24 amplification, and mitochondrion-related genes were enriched in patients with chr.17q21-24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species. Mouse xenograft models showed that inhibition of PDK2 with cisplatin inhibited tumor growth. This evidence suggests that targeting mitochondrial metabolism and redox homeostasis is an attractive therapeutic strategy for improving drug sensitivity in ovarian CCC

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC

<症例>胃癌手術 (脾摘術合併胃全摘術) 後の門脈血栓症の1例

A 48-year-old woman underwent total gastrectomy, splenectomy, and distal pancreatectomy with en bloc regional lymph node dissection for gastric carcinoma. Dull pain in the right upper quadrant and the back developed postoperatively. Contrast-enhanced computed tomography and ultrasonography disclosed portal vein thrombosis (PVT). Heparin and urokinase were given in conjunction with antbiotics. This treatment resulted in clinical improvement, but failed to achieve complete thrombolysis. Cavernous transformation of the portal system was confirmed. Although PVT after splenectomy has been reported mainly in patients with hematological disorders, our case suggests that splenectomy for en bloc node dissection in gastric carcinoma is a possible cause of PVT.門脈血栓症は肝硬変や肝癌の患者で時に認められる病態であるが, 術後の門脈血栓症は稀であり, そのほとんどが脾腫に対する脾摘術後に発生している. 我々は胃癌根治術に伴う脾摘術後に門脈血栓をきたした症例を経験したので報告する. 症例は48才の女性で, 胃体上部後壁を中心とする5型胃癌に対し, 胃全摘術, 脾摘術, 膵尾側切除術を行なった. 病変は組織学的には低分化腺癌, 深達度ss, No, Po, Ho の stage I b で, 摘出した脾重量は 150g であった. なお, 術前の出血凝固系検査には異常を認めなかった. 術後18日目より右上腹部から背部の鈍痛が出現し, 白血球数, CRP, 血清アルカリフォスファターゼ値も上昇してきた. 術後19日目の造影CTで, 門脈, 上腸間膜静脈がほとんど造影されず, 門脈から上腸間膜静脈におよぶ血栓形成が考えられた. 抗生剤の投与とともにただちにへパリンの持続静注とウロキナーゼ投与を併用したところ, 臨床症状や検査所見は軽快した. ただし, 血栓は完全に消失せず, その後の腹部血管造影では側副血行路としての肝十二指腸間膜内の静脈拡張, いわゆるcavernous transformation が認められた. へパリン, ウロキナーゼの投与からワーファリン内服に切り替え, 患者は術後66日目に退院した. 現在, 術後2年経過したが, 食道静脈瘤の出現や消化管出血などの門脈血栓, 門脈圧充亢進に起因すると思われる症状は認めていない. 我々の症例は, 進行胃癌根治術の際にしばしは合わせ行われる脾摘術後にも門脈血栓症の出現する可能性があることを示唆しており, そのような手術を受けた患者が術後原因不明の腹部症状や白血球増加を来たした時には門脈血栓症も疑い精査を進める必要があると考えられる

Expectant management of a herniated amniotic sac presenting as silent uterine rupture: a case report and literature review.

Foetal membranes bulging into the abdominal cavity is a unique initial manifestation of silent or complete uterine rupture during pregnancy. Since silent uterine rupture has potential risk for complete uterine rupture, which leads to acute life-threatening complications for both the mother and baby, it is difficult to determine whether to manage expectantly or surgically, including repair of the uterine wall or termination of the pregnancy, especially in the early second trimester. We present here a case of a herniated amniotic sac with overstretched uterine wall of the fundus presenting as silent uterine rupture, which was incidentally detected on routine ultrasonography at 18 weeks' gestation in a 38-year-old primigravida with a history of myomectomy for diffuse uterine leiomyomatosis. Magnetic resonance imaging examination revealed that the myometrium thickness was fully maintained at the site of the foetal membranes ballooning. The pregnancy was therefore managed expectantly and continued to successful delivery at 30 weeks' gestation. The precise assessment of the uterine wall may be essential to manage a herniated amniotic sac presenting as silent uterine rupture and to optimise the outcome of the pregnancy. We review all cases of a herniated amniotic sac out of focally overstretched uterine wall before 34 weeks' gestation

Low-Grade Endometrial Stromal Sarcoma with a Nodule-in-Nodule Appearance in Preoperative Magnetic Resonance Images

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignant disease and demonstrates various patterns in preoperative imaging. Therefore, accurate diagnosis is important. Given its unique form, we report a case of LG-ESS with a nodule-in-nodule appearance on preoperative imaging. A 41-year-old woman was referred to our department for further examination of a 45 mm diameter uterine corpus mass. Preoperative magnetic resonance imaging (MRI) revealed several small nodules within a larger nodule. T2-weighted images showed moderate-to-high signal intensity with focal bands of low signal intensity in the small nodules. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathological findings of the small nodules showed densely concentrated endometrial stromal cells reminiscent of a proliferative phase endometrium with a concentric arrangement of small spiral arteriole-like vessels. The small nodules exhibited an expansile growth pattern and were surrounded by less densely concentrated endometrial stromal cells intermingled with the normal uterine myometrium. LG-ESS with smooth muscle differentiation and sex cord-like elements was partially observed. In summary, LG-ESS demonstrating a unique nodule-in-nodule appearance on preoperative imaging histopathologically comprised tumor cells of varying densities. Our current case suggests that preoperative diagnostic imaging with MRI may be useful

Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC