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1. Twist Expression Predicts Poor Clinical Outcome of Patients with Clear Cell Carcinoma of the Ovary

Author

Hiroaki Kajiyama, Fumitaka Kikkawa, Eiko Yamamoto, Akihiro Nawa, Satoyo Hosono, Seiji Nomura, Kiyosumi Shibata, Mikio Terauchi, and Kazuhiko Ino

Subjects
Adult, Cancer Research, Pathology, medicine.medical_specialty, Biology, Disease-Free Survival, Twist transcription factor, Predictive Value of Tests, Cell Line, Tumor, Biomarkers, Tumor, medicine, Humans, Clinical significance, Twist, Survival rate, Aged, Ovarian Neoplasms, Twist-Related Protein 1, Anatomical pathology, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Rate, Oncology, Multivariate Analysis, Clear cell carcinoma, Disease Progression, Cancer research, Adenocarcinoma, Immunohistochemistry, Female, Adenocarcinoma, Clear Cell
Abstract

Objectives: Twist is a highly conserved basic helix-loop-helix transcription factor that regulates the expression of E-cadherin and promotes the epithelial-mesenchymal transition, which is critical for tumor infiltration. We examined the distribution and expression of this molecule in clear cell carcinoma of the ovary (CCC) to elucidate their clinical significance. Methods: Paraffin sections from CCC tissues (n = 27) were immunostained with Twist antibody and staining intensities were evaluated. Stratified with various clinicopathological factors, overall survival (OS) and progression-free survival (PFS) were evaluated. Results: In the 27 carcinomas, negative Twist immunoexpression was observed in 14 cases (51.9%), and positive immunoexpression in 13 (48.1%). Twist, when categorized into negative versus positive expression, was associated with FIGO stage and peritoneal cytology. In addition, positive Twist expression significantly predicted a poorer OS and PFS compared with negative expression (p < 0.0001). Furthermore, the multivariate analyses revealed that positive Twist expression was an independent prognostic factor for OS and PFS of patients with CCC in this study (p = 0.0077 and 0.0033, respectively). Conclusion: The current findings suggest that the assessment of Twist immunoreactivity may be a useful prognostic indicator and that Twist may play a critical role in the progression of CCC.

Published
2006

2. Subject Index Vol. 71, 2006

Author

Maurizio Bifulco, Inés de Torres, Lara Maria Pasetto, G. Ascione, Bruno Costa, Aziz Karaoglu, Graziella Pinotti, Francesco Perrone, Yoshihiko Maehara, Giovanni Marini, Hai-Rong Wang, J.-M. Ferrero, Deling Yin, V. Georgoulias, Ramya Varadarajan, Roberto Bordonaro, Federica Papi, B. Navalpotro, Eiko Yamamoto, S. Agelaki, Jordi Giralt, Yasuhiro Ito, Daniela Massi, E. Chamorey, Tsunehiro Oyama, Gabriella Ferrandina, Roberto Buzzoni, N. Vardakis, Roberto Sorio, Nancy Watroba, Bagi R. Janarthanan, L. Frigerio, I. Raoust, S. Zonato, Huaiping Wang, Yogeshwer Shukla, Hideyuki Murata, Santiago Ramón y Cajal, Akira Miyauchi, Sandro Barni, Enrico Aitini, Roberto Labianca, Jihnhee Yu, Giulia Lo Russo, Paolo Scollo, Dionyssios Katsaros, Makoto Kammori, Madhulika Singh, Toru Tase, Motoki Nagata, M. Lallement, N. Kentepozidis, Kiyosumi Shibata, M. Takenoyama, F. Ettore, Michela Ballardini, Toru Takano, Laura Cerezo, Menotti Calvani, Pierfranco Conte, Tadao Takano, Takeshi Hanagiri, Sandro Pignata, Salvatore Palazzo, Giampietro Gasparini, Steven S.S. Poon, Giovanna Scarfone, C. Chapellier, Satoru Iida, Hiroaki Kajiyama, Genny Leporatti, Maurie Markman, D. Marussi, Ren-Rong OuYang, Fang-Yuan Chen, Hiroyuki Tsuji, Rossella Lauria, A. Karampeazis, Serena Sestini, Chun-Hong Gu, Eduardo Hermosilla, Stephen B. Edge, Valter Torri, Maria Di Bartolomeo, Yongping Cai, Torello Lotti, Seiji Nomura, L. Uziel, G. Favalli, Yo-ichi Yamashita, Franco Odicino, Hideki Tokunaga, Junko Aida, Neetu Kalra, Luigi Dogliotti, S. Oldani, D. Ferrari, Akihiro Nawa, V. Reyes, Alessandra Vernaglia Lombardi, A. Luciani, Manuel de las Heras, Giuseppe Schieppati, Yosuke Kuroda, Kosei Yasumoto, Marina Cazzaniga, Giuseppe Comella, Luigi Selvaggi, Benedetta D'Attoma, Koichi Tomoda, Manel Armengol, Emilio Bajetta, Yuhua Zhang, Mikio Terauchi, Liliana Mereu, E. Papadimitraki, Antonella Orlando, Arpine Gevorgyan, Erkan Topkan, Toshio Yamashita, Erminia Ferrario, D. Mavroudis, Sahdeo Prasad, Shinji Itoh, Rie Kurabayashi, Yuichi Wada, Luigi Manzione, Kazuhiko Ino, Fumitaka Kikkawa, Mario Dini, Hidekazu Yamada, L. Vamvakas, Antonio Ardizzoia, Hua Zhong, Toshiya Inoue, Naotaka Izumiyama, Kiyoshi Ito, Enrico Breda, Giovanna Magni, I. Peyrottes, Nobuo Yaegashi, Yoko Takagi, Vincenzo De Giorgi, Hiroyuki Uetake, Silvana Chiara, Jian-Yi Zhu, Yuzo Shimode, Hironobu Sasano, Kenji Nagata, Jun Ichi Akahira, Donato F. Altomare, Akira Sato, Dotti Katia, Kenichi Sugihara, Ryuji Ohta, Satoyo Hosono, Hisaya Yukawa, A. Courdi, I. Gioulbasanis, Keiji Kato, Sergi Benavente, Kosuke Yoshinaga, Bruno Massidda, Uma Singh, Kenji Sugio, C. Balu-Maestro, Hitoshi Niikura, S. Caldiera, Xiaofang Zhang, Salvatore Tumolo, Anna Maria Bochicchio, E. Espin, Stefano Cascinu, Dai Kitagawa, Gengyin Zhou, Shinji Morita, Luigi Mariani, Giovanna Marforio, Akinobu Taketomi, Giovanni Cicero, Mitsuhiko Kashio, Maria Gabriella Caruso, Fulan Wei, Ken-ichi Nakamura, Jie-Yin Han, Nicoletta Zilembo, Fabio Ghezzi, Masafumi Toyoshima, Michio Kaminishi, Takayoshi Kiba, Tadahiro Nozoe, Shinichi Aishima, Satoru Nagase, R. Largillier, P. Foa, M. Ignatiadis, and Maria Notarnicola

Subjects
Cancer Research, Index (economics), Oncology, Statistics, Subject (documents), General Medicine, Mathematics
Published
2006

3. Contents Vol. 71, 2006

Author

Roberto Buzzoni, Bagi R. Janarthanan, A. Luciani, Manuel de las Heras, Eiko Yamamoto, Roberto Sorio, Nancy Watroba, Genny Leporatti, Makoto Kammori, D. Marussi, Koichi Tomoda, Uma Singh, Yosuke Kuroda, I. Raoust, A. Karampeazis, Yongping Cai, Hiroyuki Tsuji, G. Ascione, Takeshi Hanagiri, Chun-Hong Gu, Eduardo Hermosilla, Valter Torri, G. Favalli, S. Oldani, Luigi Selvaggi, Toru Takano, Laura Cerezo, Motoki Nagata, Kenji Sugio, C. Balu-Maestro, Vincenzo De Giorgi, Yoshihiko Maehara, Deling Yin, Giovanni Marini, Toshiya Inoue, J.-M. Ferrero, M. Lallement, Tsunehiro Oyama, Kiyoshi Ito, Santiago Ramón y Cajal, Gabriella Ferrandina, N. Kentepozidis, Toru Tase, N. Vardakis, C. Chapellier, Ramya Varadarajan, B. Navalpotro, Akihiro Nawa, V. Georgoulias, Dionyssios Katsaros, Kosei Yasumoto, Akira Sato, Dotti Katia, Michio Kaminishi, M. Takenoyama, F. Ettore, Menotti Calvani, Huaiping Wang, Satoru Iida, Hiroaki Kajiyama, Fang-Yuan Chen, Jihnhee Yu, Maurie Markman, Akira Miyauchi, Sandro Barni, Seiji Nomura, Pierfranco Conte, Paolo Scollo, Liliana Mereu, Madhulika Singh, E. Papadimitraki, S. Caldiera, V. Reyes, Alessandra Vernaglia Lombardi, Benedetta D'Attoma, Satoru Nagase, Maria Di Bartolomeo, Ren-Rong OuYang, L. Frigerio, E. Chamorey, Giovanna Magni, S. Zonato, Antonella Orlando, Rossella Lauria, I. Peyrottes, Maria Gabriella Caruso, Yogeshwer Shukla, Jie-Yin Han, Luigi Manzione, Mario Dini, Hiroyuki Uetake, Nobuo Yaegashi, Nicoletta Zilembo, Keiji Kato, Steven S.S. Poon, Giovanna Scarfone, L. Vamvakas, Toshio Yamashita, Shinji Itoh, Rie Kurabayashi, Yuichi Wada, Jian-Yi Zhu, Stephen B. Edge, L. Uziel, Sergi Benavente, Fumitaka Kikkawa, Hidekazu Yamada, S. Agelaki, Tadao Takano, Kenichi Sugihara, Roberto Labianca, Giulia Lo Russo, Neetu Kalra, Giuseppe Schieppati, Erminia Ferrario, Hideyuki Murata, Torello Lotti, Marina Cazzaniga, Giuseppe Comella, I. Gioulbasanis, Silvana Chiara, Michela Ballardini, Yuzo Shimode, Kosuke Yoshinaga, Bruno Massidda, Hironobu Sasano, Junko Aida, Serena Sestini, Roberto Bordonaro, Luigi Dogliotti, D. Mavroudis, Yoko Takagi, Franco Odicino, Mikio Terauchi, Jun Ichi Akahira, Manel Armengol, Ryuji Ohta, Sandro Pignata, Kenji Nagata, Federica Papi, Enrico Aitini, Jordi Giralt, Hideki Tokunaga, Arpine Gevorgyan, Kazuhiko Ino, Satoyo Hosono, Hisaya Yukawa, A. Courdi, Akinobu Taketomi, Hua Zhong, Bruno Costa, Giovanni Cicero, Mitsuhiko Kashio, Maria Notarnicola, Ken-ichi Nakamura, Maurizio Bifulco, Donato F. Altomare, Fabio Ghezzi, Masafumi Toyoshima, Dai Kitagawa, Inés de Torres, Lara Maria Pasetto, Enrico Breda, Gengyin Zhou, Graziella Pinotti, Luigi Mariani, Giovanna Marforio, Salvatore Palazzo, Giampietro Gasparini, M. Ignatiadis, Tadahiro Nozoe, Shinichi Aishima, Takayoshi Kiba, Erkan Topkan, Sahdeo Prasad, Aziz Karaoglu, R. Largillier, P. Foa, Fulan Wei, Yasuhiro Ito, Antonio Ardizzoia, Naotaka Izumiyama, Salvatore Tumolo, Kiyosumi Shibata, Anna Maria Bochicchio, E. Espin, Stefano Cascinu, Yo-ichi Yamashita, Hitoshi Niikura, Hai-Rong Wang, D. Ferrari, Daniela Massi, Xiaofang Zhang, Emilio Bajetta, Yuhua Zhang, Shinji Morita, and Francesco Perrone

Subjects
Cancer Research, Oncology, General Medicine
Published
2006

4. Combination Effect of Anti-Fas Antibody and Chemotherapeutic Drugs in Ovarian Cancer Cells in vitro

Author

Yasunori Wakahara, Fumiyo Wakahara, Nobuhiko Suganuma, Fumitaka Kikkawa, Yutaka Tomoda, Akemi Hayakawa, Tomomitsu Okamoto, and Akihiro Nawa

Subjects
Cancer Research, Genital Neoplasms, Female, medicine.medical_treatment, Biology, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, medicine, Humans, fas Receptor, Etoposide, Ovarian Neoplasms, Cisplatin, General Medicine, Immunotherapy, Fas receptor, medicine.disease, Combined Modality Therapy, Gene Expression Regulation, Neoplastic, Oncology, Cell culture, Apoptosis, Immunology, biology.protein, Cancer research, Female, Antibody, Ovarian cancer, medicine.drug
Abstract

To clarify the significance of the Fas antigen (Ag) in gynecologic tumors, its expression in gynecologic cancer cell lines was examined. The Fas Ag was expressed in 6 of 15 cell lines. Five of 8 ovarian cancer cell lines but none of 4 choriocarcinoma cell lines expressed the Fas Ag. In drug-resistant cell lines derived from one of the Fas-positive cells, its expression was not lost after development of resistance to cisplatin, SN-38 or etoposide, but its expression was absent in the cell line resistant to Adriamycin. The effect of the anti-Fas antibody (Ab) was then studied. Apoptosis was induced in 7 of 9 Fas-positive cell lines, whereas the remaining two cell lines were unaffected. Furthermore, the combination effect of the anti-Fas Ab and drugs was examined in an ovarian cancer cell line and its drug-resistant variants, and a synergistic effect was observed. These results suggest important roles of the Fas Ag in ovarian cancer and the potential for overcoming drug resistance by a combination of the anti-Fas Ab and various drugs.

Published
1997

5. Establishment and characterization of an ovarian yolk sac tumor cell line reveals possible involvement of Nkx2.5 in tumor development

Author

Hiroaki Kajiyama, Kazuhiko Ino, Mikio Terauchi, Kiyosumi Shibata, Eiko Yamamoto, Akihiro Nawa, and Fumitaka Kikkawa

Subjects
Adult, endocrine system, Cancer Research, medicine.medical_specialty, endocrine system diseases, Transplantation, Heterologous, Mice, Nude, Biology, medicine.disease_cause, Ovarian tumor, Mice, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, Yolk sac, RNA, Small Interfering, Cisplatin, Homeodomain Proteins, Ovarian Neoplasms, Endodermal Sinus Tumor, General Medicine, medicine.disease, female genital diseases and pregnancy complications, Transplantation, Endocrinology, medicine.anatomical_structure, Oncology, Cell culture, embryonic structures, Cancer research, Homeobox Protein Nkx-2.5, Female, Germ cell tumors, Carcinogenesis, Ovarian Yolk Sac Tumor, medicine.drug, Transcription Factors
Abstract

Objective: Ovarian yolk sac tumor (YST) is rare and highly malignant. Up to the present, there have been no cell lines of human ovarian YST constructed and, therefore, no studies on their cell function. The purpose of this study was to establish a human ovarian YST cell line to be able to identify a target for novel molecular-based therapy. Methods: A 28-year-old woman underwent right salpingo-oophorectomy for right ovarian YST. YST cell lines (NOY1 and NOY2) were established from surgical specimens, and NOY1 cells were characterized. We also transfected them with small interfering RNA (siRNA) oligonucleotides specific for human Nkx2.5 and investigated cell proliferation compared to control siRNA-transfected cells. Results: The cell lines were successfully maintained both in culture and in nude mice. Histological examination showed that xenografted tumors were composed of cells in solid and glandular patterns of YST. These cells were positively immunostained for AFP. Nkx2.5 siRNA-transfected NOY1 cell viability decreased by 50% compared to that of control-siRNA-transfected cells. Conclusions: This is the first report of a cell line established from human YST. Analysis of this new cell line suggested that Nkx2.5 can be a new molecular target in the treatment of ovarian YST.

Published
2007

6. Usefulness of granulocyte colony-stimulating factor on neutropenia in patients of invasive mole and choriocarcinoma

Author

Takanobu Suzuki, Kazuhiko Ino, Toru Nakanishi, Yutaka Tomoda, Setsuko Goto, Noriko Kato, Akihiro Nawa, and Tomomitsu Okamoto

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Neutropenia, medicine.medical_treatment, Antineoplastic Agents, Gastroenterology, Chorioepithelioma, Pregnancy, Internal medicine, White blood cell, Granulocyte Colony-Stimulating Factor, Tumor Cells, Cultured, Medicine, Humans, Choriocarcinoma, Retrospective Studies, Chemotherapy, business.industry, Gestational trophoblastic disease, Hydatidiform Mole, Invasive, Combination chemotherapy, General Medicine, Middle Aged, medicine.disease, Granulocyte colony-stimulating factor, Endocrinology, medicine.anatomical_structure, Oncology, Uterine Neoplasms, Female, business, Cell Division
Abstract

The effect of human granulocyte colony stimulating factor (hG-CSF) was investigated on the proliferation of choriocarcinoma cells in vitro. No growth-stimulating effect was observed. Then, 22 patients with invasive mole and 9 patients with choriocarcinoma who received combination chemotherapy were treated with hG-CSF when white blood cell counts decreased below 2,000/mm3. The duration of neutropenia was reduced significantly by 3-4 days with the use of hG-CSF. No side effects were observed. These results indicate safety and usefulness of hG-CSF as an adjunct to chemotherapy in the treatment of gestational trophoblastic disease.

Published
1995

7. Positive correlation between cytochrome P450 2E1 mRNA level and serum estradiol level in human uterine endometrium

Author

Yutaka Tomoda, Nobuhiko Suganuma, Michiyasu Kawai, Akihiro Nawa, Hidenori Oguchi, Toshifumi Aoyama, Osamu Maeda, and Fumitaka Kikkawa

Subjects
Adult, Cancer Research, medicine.medical_specialty, Cytochrome, Molecular Sequence Data, urologic and male genital diseases, Endometrium, digestive system, Polymerase Chain Reaction, chemistry.chemical_compound, Cytochrome P-450 Enzyme System, Internal medicine, medicine, Humans, heterocyclic compounds, RNA, Messenger, Carcinogen, DNA Primers, chemistry.chemical_classification, Messenger RNA, biology, Base Sequence, Estradiol, Leiomyoma, Cytochrome P-450 CYP2E1, Oxidoreductases, N-Demethylating, General Medicine, respiratory system, CYP2E1, Middle Aged, Molecular biology, enzymes and coenzymes (carbohydrates), medicine.anatomical_structure, Endocrinology, Enzyme, Oncology, chemistry, Liver, Uterine Neoplasms, biology.protein, Female, Primer (molecular biology), Hemangioma, DNA
Abstract

Most carcinogens are bioactivated by cytochrome P450s (CYPs) and these enzymes within target cells are closely related to susceptibility to cancer. Since extrahepatic CYPs occur typically at much lower levels, the existence and the role of CYP in extrahepatic tissues have been difficult to assess. In this study, we modified the reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the relative quantities of CYP 2E1 mRNA in human endometrium. Total RNA from human endometrium was reverse-transcribed and co-amplified by PCR in the same tube containing both primer pairs of CYP 2E1 and beta-actin. The CYP 2E1 and beta-actin PCR products were 298 and 600 bp, respectively. The restriction enzyme MboI digested these two products to the predicted size for DNA fragments, demonstrating that both PCR products were specific and CYP 2E1 mRNA exists in human endometrium. CYP 1A1 mRNA was also examined, but could not be detected clearly. Adding [alpha-32P]dCTP to the reaction mixture made it possible to quantify the relative yield of the CYP 2E1 PCR product in comparison with the beta-actin product. The ratio of the yield of the CYP 2E1 PCR product to the beta-actin PCR product could be calculated at a point of 25 cycles of amplification. This ratio and serum estradiol levels were correlated positively (r = 0.654; p0.05), but no relationship to serum progesterone levels was observed.

Published
1994

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