生水 真紀夫

Metastasis of ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination is uncommon. A 63-year-old woman underwent surgery for a clear cell adenocarcinoma of the ovary and received adjuvant chemotherapy. Eighteen months after the operation, she presented with recurrent occult bowel hemorrhage without evidence of an abdominal mass. Nine months later, a rapidly growing abdominal mass was detected. Laparoscopy revealed a solitary tumor of the ileum covered with an intact serosal layer. Partial ileectomy was performed for tumor resection. Histological examination revealed cells resembling the primary ovarian tumor in the mucosal surface of the small bowel along with an intact serosa. The tumor cells were positive for cytokeratin 7 and negative for cytokeratin 20, suggesting an ovarian origin. This is the first report of solitary metastasis of an ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination. Metastasis to the small bowel should be considered in ovarian carcinoma patients with occult gastrointestinal hemorrhage. © 2011 Japan Society of Obstetrics and Gynecology.

アロマターゼはエストロゲン合成に必須の酵素であり、生殖生理機能に重要な役割を果たしている。エストロゲンの作用には、血中を介して遠隔の標的臓器に及ぼす内分泌作用と、末梢組織で合成されてその近傍で作用するパラクリン・オートクリン作用とがある。最近では、卵巣においても後者の役割が注目されている。

Based on the microRNA (miRNA) expression signatures of hypopharyngeal and esophageal squamous cell carcinoma, we found that miR-1 was significantly down-regulated in cancer cells. In this study, we investigated the functional significance of miR-1 in head and neck squamous cell carcinoma (HNSCC) cells and identified miR-1-regulated novel cancer pathways. Gain-of-function studies using miR-1 revealed significant decreases in HNSCC cell proliferation, invasion, and migration. In addition, the promotion of cell apoptosis and cell cycle arrest was demonstrated following miR-1 transfection of cancer cells. A search for the targets of miR-1 revealed that transgelin 2 (TAGLN2) was directly regulated by miR-1. Silencing of TAGLN2 significantly inhibited cell proliferation and invasion in HNSCC cells. Down-regulation of miR-1 and up-regulation of TAGLN2 were confirmed in HNSCC clinical specimens. Our data indicate that TAGLN2 may have an oncogenic function and may be regulated by miR-1, a tumor suppressive miRNA in HNSCC. The identification of novel miR-1-regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC carcinogenesis. © Nohata et al.

Aromatase, a key enzyme of estrogen biosynthesis, is transcriptionally regulated by many growth factors. IGF-I enhances aromatase activity in a variety of cells, but the mechanism of action has not been determined. We herein report our finding of a novel mechanism of action for IGF-I. IGF-I enhanced the dexamethasone (DEX)-induced aromatase activity by 30% in serum-starved THP-1 cells. The increase was associated with a corresponding increase in the level of aromatase protein but not with any change in the mRNA level. Metabolic labeling experiments revealed that IGF-I inhibited the degradation of aromatase. We identified pepstatin A as the most effective inhibitor of aromatase degradation by in vitro assay. Using a nontoxic concentration of pepstatin A, we examined IGF-I's action on aromatase distribution in microsomes and lysosomes. In the presence of pepstatin A, DEX caused an increase in the amount of aromatase in both microsomes and lysosomes, and IGF-I attenuated the DEX-induced accumulation of aromatase in lysosomes and, conversely, enhanced its accumulation in the microsomes. The addition of serum abolished the IGF-I-induced changes. The transport from microsome to lysosome was fluorescently traced in cells using a recombinant aromatase. IGF-I selectively reduced the aromatase signal in the lysosomes. Finally, we observed that IGF-I enhanced the aromatase activity by 50% as early as 1 h after treatment; furthermore, rapamycin, an enhancer of autophagy, completely negated the effect of IGF-I on the enzyme. These results indicate that IGF-I enhances aromatase by the inhibition of autophagy. (Endocrinology 151: 4949-4958, 2010)

AIM: To determine the effectiveness of postoperative concurrent daily low-dose cisplatin-based chemoradiation (CCRT) in patients with high-risk cervical cancer. PATIENTS AND METHODS: Patients with stage IB, IIA, or IIB cervical cancer who were initially treated with radical hysterectomy and pelvic lymphadenectomy, and were proven to have pelvic lymph node metastasis (pN1) or microscopic involvement of the parametrium (pT2b), participated in this study. Thirty-one patients received adjuvant CCRT with daily low-dose (6-8.5 mg/m(2)) cisplatin (daily CCRT group). A non-randomised control group of 44 patients received adjuvant radiotherapy alone (RT group). RESULTS: Overall survival (OS) at 4 years was 61% in the RT group and 91% in the daily CCRT group (p=0.004). Hazard ratio for poorer recurrence-free survival (RFS) in the RT group vs. the CCRT group was 7.9 (p=0.006). In the daily CCRT group, daily cisplatin chemotherapy was successfully completed in 27 out of 31 patients, although toxicity of grade >or=3 was found in 29% for neutropenia and 17% for gastrointestinal tract toxicity. CONCLUSION: Postoperative adjuvant CCRT with daily low-dose cisplatin improved RFS and OS of pT2b or pN1 patients, with acceptable compliance.

ゴナドトロピン放出ホルモン(Gn-RH)受容体変異は、ゴナドトロピン単独欠損症(IHH)の原因である。ミスセンス変異遺伝子のホモ接合や複合ヘテロ接合例が大部分を占めている。ヘテロ接合例では臨床症状を呈さない。変異受容体の発現実験から、変異の種類により受容体機能低下の程度が異なることが明らかにされている。受容体機能低下が強い変異をもつ患者では、臨床症状もより強い傾向がみられる。変異受容体は、立体構造の変化から合成後に細胞膜に運ばれることなく分解される、すなわち、フォールディング異常により機能低下をきたす。非ペプチド性Gn-RH受容体アンタゴニストにより変異受容体のフォールディングが助けられ、細胞膜への発現、リガンド結合能、シグナル伝達は部分的に回復することがわかってきた。(著者抄録)

Background: To report the cytologic characteristics of low grade endometrial stromal sarcoma with sex cord-like differtiation. Case: A 49 year-old woman presented with hypermenorrhea, menorrhalgia and anemia. With a diagnosis of degenerated leiomyoma of the uterus, simple total hysterectomy was conducted. Histologic examination revealed cells with ovoid to short, spindle-shaped nuclei resembling endometrial stromal cells proliferating in a space-occupying manner and compressing and partially infiltrating the myometrium. Some tumor cells were arranged in sex cord-like form, and hyalinization was observed in the center of the cord. Low grade endometrial stromal sarcoma with sex cord-like differentiation was diagnosed. Touch imprint cytologic examination of the tumor showed cells containing scanty cytoplasm and ovoid to spindle-shaped nuclei with little atypia they were scattered individually, aggregated in clusters, or arranged in cord glandular form. Hyaline-like substance was present in abundance. The histologic characteristics of the endometrial stromal sarcoma with sex cord-like differentiation were confirme by touch imprint cytology of the tumor. Conclusion: In this case of low grade endometrial stromal sarcoma with sex cord-like differentiation, cytologic examination revealed hyaline substance and tumor cells aligned in cord or glandular form. © The International Academy of Cytology.

前置癒着胎盤における帝王切開術は大量出血をきたす代表的な産科手術である。今回我々は、術中出血量の軽減を図ることを目的に、Intra-aortic balloon occlusion(IABO)を、前置胎盤の帝王切開術に使用しその有用性について検討した。対象は、最近1年半の間に当科で経験した、大量出血が予想された前置胎盤4症例である。腎動脈分岐部下の腹部大動脈でバルーンを拡張させ、術中最も出血量が増加すると思われるタイミングで1回につき最長20分間の血流遮断を行なった。偶発的にバルーンが虚脱した1例と比較して、他の3例の術中出血量は明らかに少なかった。IABOが前置癒着胎盤症例における周術期出血量低減に有用な手技となり得る可能性が示唆された。(著者抄録)

We describe a case of placental surface cyst. Intrauterine growth restriction or maternal floor infarction occurs in about 10% of cases [Brown DL, DiSalvo DN, Frates MC, et al. Placental surface cysts detected on sonography: histologic and clinical correlation. J Ultrasound Med. 2002 21(6):641-8]. Large or multiple cysts seem to have a higher frequency of these complications. To the best of our knowledge, there are a few reports about MR imaging of placental surface cysts. © 2009 Elsevier Ireland Ltd. All rights reserved.

エストロゲンの作用には,genomic actionとnon-genomic actionの2つがある。前者は,エストロゲンが細胞質内でエストロゲン受容体と結合した後,DNAに結合して転写を亢進させるもので,タンパク合成を介するため作用の発揮に数時間を要する。後者は,膜型受容体にエストロゲンが結合した後,MAPKなどのシグナル伝達系を活性化させて数秒から数分で作用を発揮するものである。SERMs(selective estrogen receptor modulators)は,エストロゲン受容体に結合して作用を発揮するが,エストロゲンとの立体構造の違いから,エストロゲンとは異なる作用スペクトラムを示す。治療効果の増強と副作用の軽減を目指し,さまざまなSERMsが開発されている。(著者抄録)

Estrogen deficiency in postmenopausal women causes climacteric symptoms and signs and progresses cardiovascular diseases, dyslipidemia and osteopenia. Hormone replacement therapy (HRT) or just estrogen replacement therapy (ERT) is used to diminish these menopausal symptoms and signs and help prevent subsequent medial problems. Use of hormone replacement therapy by postmenopausal women, however, increases the risk of breast cancer and thromboembolic diseases, and also the risk of cardiovascular events when HRT is started over 60 years old.