Bin Takeda

Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro

The effect of methotrexate (MTX) on the growth and human chorionic gonadotropin (hCG) secretion of five gestational and two nongestational human choriocarcinoma cell lines was studied in vitro. A striking heterogeneity in hCG secretion was noted among the cell lines. The growth of cells which secreted large quantities of hCG, such as HCCM-5, BeWo, and IMa, was inhibited by continuous exposure to 2 X 10(-8)M MTX. In contrast, cells which secreted little hCG, such as SCH, ENAMI-1, and GCH-1, showed no response to the growth inhibitory action of 2 X 10(-8)M MTX and the 3H-thymidine uptake was not reduced by treatment with MTX at doses of up to 10(-4)M for 48 hours. The common morphologic alterations observed in the cells which responded to MTX were an increase in the number of multinucleated giant cells, the appearance of vacuoles and granules in the cytoplasm, and enlargement of the nuclei. Increased hCG secretion was observed in accordance with the appearance of such morphologically altered cells. Part of the mechanisms of resistance to MTX appeared to involve both impairment of MTX uptake by the cells and an increase in the level of intracellular dihydrofolate reductase.

Morphologic and enzyme-cytochemical changes in uterine adenocarcinoma cells of a rat by direct application of progesterone in vitro

Abstract HTP/C1/P8 culture, a subclonal cell line of HTP/C1 culture derived from a rat uterine adenocarcinoma, has been subcultivated in a culture medium containing progesterone, 8 μg/ml. HTP/C1/P8 cells revealed a more differentiated form by light and electron microscopy, compared with original HTP/C1 cells growing in a culture medium without progesterone. The effect of progesterone on these uterine adenocarcinoma cells seemed to be direct, as evidenced by the significantly higher uptake of [ 3 H]progesterone into the cells in vitro . Enzyme-cytochemical changes of the cells by the direct application of progesterone is discussed in relation to the morphologic differentiation of these cells.

Effect of ovariectomy, adrenalectomy, and hypophysectomy on carcinogenesis of the endometrium by 7,12-dimethylbenz[a]anthracene in rats

The incidence of hyperplasia and carcinoma of the endometrium in rats by direct application of 7,12-dimethylbenz[a]anthracene to the uterine horn was suppressed in ovariectomized (ovx) and hypophysectomized (hypox) rats compared with that in nonoperated control and adrenalectomized (adx) rats. Since the values of serum estrone and estradiol in ovx and hypox rats were significantly (P < 0.02; Students t test) lower than those in nonoperated and adx rats, it was suggested that endogenous estrogen might play an essential role in endometrial carcinogenesis by a chemical carcinogen.

Endometrial carcinoma following chronic anovulation in a premenopausal woman with systemic lupus erythematosus

Endometrial carcinoma was diagnosed in a premenopausal woman suffering with systemic lupus erythematosus. She had received both predonisolone and an im‐munosuppressive agent for more than 10 years. Anovulatory cycles persisted during drug administration, along with dysfunctional uterine bleeding. The serum estrogen: progesterone ratio was high. Repeated endometrial biopsies revealed a progression of change from benign proliferation to cystic hyperplasia, adenomatous hyperplasia, atypical hyperplasia and invasive adenocarcinoma. These clinical data suggest that a result of long‐term unopposed endogenous estrogen can have been the cause of the endometrial carcinoma.

Benign & malignant breast diseases with intraductal epithelial proliferation with special reference to a comparison of cytological features on fine needle aspiration biopsy.

乳腺穿刺吸引細胞診を行い細胞量が豊富に採取されたが, 個々の細胞が小円形を示し, 良悪の鑑別が困難であった良性病変10例 (上皮増生の強い線維腺腫, 乳管過形成を伴う乳腺症, 乳管内乳頭腫), 悪性腫瘍20例 (非浸潤性乳管癌, 乳管内増殖優位な乳頭腺管癌および充実腺管癌) について, その細胞像を検討した.(1) 良性病変では背景に間質成分, 裸核状細胞 (線維芽細胞) をみることが多い. 個々の上皮細胞は結合性が強く, 散在性に乏しい. また核形不整に乏しく, 染色質は細顆粒状を示しやすかった.(2) 悪性腫瘍では背景に若干の塊死, 間質成分などはみるものの大部分は上皮細胞のみで個々の上皮細胞は良性病変に比べ, 結合性が弱く, 散在性に強く, 核形不整, 染色質粗顆粒状を示す傾向にあった.(3) 配列, 核大小不同, 核分裂については特に明らかな違いがみられなかった.乳管内増殖が強いこれらの病変の細胞像は小型で異型が乏しいが, 以上のように背景出現細胞, 上皮細胞の結合性, 核形, 染色質所見などを中心に詳細に検索することが大切であった.

A case of juvenile granulosa cell tumor associated with rapid malignant course.

急速な悪性経過をとった若年型顆粒膜細胞腫の1例を経験した. 症例は25歳の女性で胸・腹水を伴っていた. 腫瘍は右卵巣に発生し, その大きさ17×11×10cmで充実性と嚢胞性の部分が混在してみられた. 捺印細胞像は小円形で結合性を示す顆粒膜細胞と紡錘形で散在性を示す莱膜細胞が多数認められ, さらに少数の核偏在細胞, 細胞質が広く淡い黄体化細胞などとともにしばしば核分裂像も散見された. 成人型顆粒膜細胞腫との細胞像の違いは核溝の出現は少なく, Call-Exner小体はみられず, しぼしぼ核分裂像を認めることである. これらの細胞は免疫細胞化学的にVimentin, Desmin陽性を示した. また少数の核偏在細胞にはEstradiol陽性の所見を呈した. 電顕的にも顆粒膜細胞, 英膜細胞を確認し, その中間的細胞や線維芽細胞様細胞も認められた.臨床的経過を裏付けるように腫瘍の異常な大きさ, 細胞の核異型度, 核分裂像の多さなど組織細胞学的にも悪性が示唆された.

A case of papillary renal cell carcinoma suggested bellini duct origin. Cytological, histological, immunohistochemical and ultrastructual study.

Bellini管起源が示唆された乳頭状腎細胞癌の1例を経験した. 症例は68歳, 男性で左腎下部腫瘤の穿刺吸引細胞診では多数の泡沫細胞を背景に乳頭状, ボール状, シート状および枝状配列を示す細胞集塊を認め, その細胞異型, 核異型は乏しかった.組織学的には乳頭状の増殖を示す腎細胞癌であった. 免疫組織化学的には近位尿細管系マーカーであるLM1, LTAと遠位尿細管系マーカーであるSBA, PNA, DBA, EMAが陽性を示し, Bellini管起源が示唆された. 電顕的に腫瘍細胞は明細胞と暗細胞よりなり, 暗細胞は円柱状で多数のミトコンドリアを含んでおり, 正常腎集合管からBellini管にかけての上皮によく類似していた.

Detection of chlamydia trachomatis in urethral scraps.

Chlamydia trachomatis (C.trachomatis) は, 近年非淋菌尿道炎 (Non-gonococcal urethritis: NGU) の原因微生物として注目されているが, 細胞診断学的検索は現在まであまりなされていない. そこで, 尿道炎症状を訴えた男性93例から, 直接塗抹標本を作成し, Papanicolaou標本の細胞形態, 螢光抗体法 (IF法: Micm Trak Chlamydia Trachomatis Direct Test, Syva社), 酵素抗体法 (PAP法: クラミジア同定用キット, Ortho社) を施行し, この3者における陽性率および形態について比較検討した. また, 一方これらの症例は同時に細菌学的検索も行い, N.gonorrhoeaeと同定されたものを淋菌性尿道炎 (Gonococcal urethritis: GU) とした. その結果, Papanicolaou標本から封入体細胞は34.4%に出現したが, 封入体自体はPapanicolaou脱色後PAP法において陰性であった. また, 星雲状封入体, あるいはC.trachomatisの特徴的細胞像は認められなかった. しかし, 封入体の出現する症例は, MT法, PAP法により71.9%にC.trachomatisが陽性であった. C.trachomatisの陽性率はNGUで, MT法52.2%, PAP法36.2%であった. また, GUではMT法25.0%, PAP法33.3%が陽性であり, 淋疾後尿道炎の可能性が示唆された. さらに, MT法とPAP法の併用で陽性率は57.0%に上昇し, C.trachomatisの検出には有効と考えられた.