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- OOTR,GSK & NIPPON KAYAKU Cosponsor Programme;
Eric P Winer / Ian E Krop (Harvard University) Lecture
"Breast Cancer Treatment with Targeted Agents - Current and Future"
(28 February, 2010 Rihga Royal Hotel, Hiroshima) - OOTR Investigators Meeting (25 February, 2010 The Westin Miyako Hotel Kyoto）
- OOTR Investigators Meeting (19 February, 2009 Mandarin Oriental Hotel (Macau))
- Lecture of Prof. Aaron Ciechanover (Laureate of Nobel Prize in chemistry)
"Why our proteins have to die so we shall live?" (9 November, 2007) - OOTR Investigators Meeting (8 November, 2007)
Lecture of Prof. Aaron Ciechanover (Laureate of Nobel Prize in chemistry)
"Why our proteins have to die so we shall live?" (9 November, 2007)
Prof. Aaron Ciechanover
On the November 9th, 2007, Dr. Aaron Ciechanover, the professor of Vascular and Cancer Biology Research Center, The Rappaport Faculty of Medicine and Reserch Institute and Technion-Israel Institute of Technology, delivered a lecture entitled ‘Why our proteins have to die so we shall live?’ Many undergraduate and graduate students and medical doctors attended this special lecture. In the beginning, the professor Kohei Shiota, the dean of graduate school of medicine in Kyoto University, introduced professor Ciechanover. Dr. Masakazu Toi, the professor of the department of breast surgery, acted as a master of the lecture.
Professor Ciechanover started with the history of protein research. For a long while, it had been considered that proteins in our body wouldn’t be changed but static. Nevertheless, the conceptual changes occurred gradually since Dr. Rudolf Schoenheimer, who is the father of protein research field, discovered a method to label proteins with heavy isotope-labeled amino acids. Fifteen years later, Dr. David Hogness and Dr. Jacques Monod found that proteins within mammalian cells are dynamic. In 1955, Dr. Christian de Duve discovered the lysosome, which brought a significant change of the concept, because the cellular proteins were shown to be degraded in the lysosomes. Then, in mid-70’s, Dr. Brian Poole showed that intracellular proteins were also degraded in non-lysosomal machinery, which resulted in the discovery of ubiquitin system. In 1976, Dr. Ciechanover began intensive researches on the non-lysosomal proteolytic system.
Dr. Ciechanover’s group found that three enzymes E1, E2, and E3 are involved in the proteolysis. Ubiquitin is activated by the ubiquitin-activating enzyme (E1). An ubiquitin-conjugating enzyme (E2) transfers the activated ubiquitin moiety to the protein substrate that is bound specifically to a unique ubiquitin ligase (E3). Successive conjugation of ubiquitin moieties to one another generates a polyubiquitin chain. Unless protein substrates are marked by a polyubiquitin chain, proteases are unable to recognize.
The audience was listening intently
It is known that the ubiquitin system provides many functions, such as control of cell cycle-associated factors, regulation of signaling factors or transcriptional factors. Thereby, ubiquitin is directly involved in cell proliferation, cell death and cell differentiation. Accumulation of proteins conjugated to ubiquitin causes a variety of neurodegenerative disorders, such as Alzheimer disease, Parkinson disease, Angelman syndrome and Prader-Willi syndrome. Moreover, ubiquitin system closely links with cancer development, proliferation, invasion and resistance. In fact, ubiquitin protease inhibitor has been developed for anticancer drugs. For Instance, Bortezomib, which is able to regulate the accumulation of the abnormal proteins and inactivation of NF-kB, improves the treatment of multiple myeloma, refractory follicular non-Hodgekin lymphoma and other malignant diseases.
In the end, professor Ciechanover introduced his background that he had worked as a general surgeon about 30 years ago. Then, he concluded that ‘from bench to bedside’ is essentially important to clarify the mechanism of diseases, although it requires a great investment of time and effort. He also emphasized that the research outcomes must be returned to society. (Reported by Dr. Wakako Tsuji, Kyoto University)
OOTR Investigator's Meeting (8 November, 2007)
Senior Investigator of OOTR, Dr. Takayuki Ueno
OOTR Investigator's meeting was held at Kyoto Hotel Okura on the 8th of November. This year we have a number of new members from different countries. We have launched the OOTR institute (http://www.ootr-institute.org/) in Kyoto to promote translational research.
First, Dr. Chow introduced the new members and the OOTR institute in the meeting. After the official introduction, all members introduced themselves to facilitate the communication.
OOTR is now conducting two major clinical trials, which were discussed in the meeting. OOTR N001 trial is “Phase Ⅱ Study on the Neoadjuvant Use of Chemotherapy and Celecoxib Therapy in Patients with Invasive Breast Cancer”. Dr. Chow showed the preliminary results from the trial. OOTR N003 Study is “Randomized Trial of Docetaxel with or without Capecitabine as Neoadjuvant Chemotherapy in Female Patients with Operable Breast Cancer Who were not Observed Disease Progression after 4 cycles of 5-Fluorouracil, Epirubicin and Cyclophosphamide (FEC)”. Dr. Ohno presented the current status of the enrollment and the preliminary data from the trial. Adverse events by the combination of docetaxel and capecitabine were also discussed. How to make the accurate determination of axillary lymph node involvement was another issue for discussion.
Executive Director of OOTR, Dr. Louis W.C. Chow
Investigator of OOTR, Dr. Shinji Ohno
To create new strategies for cancer therapy, progress in translational research is inevitable. Accurate prediction of treatment efficacies and prognosis is a major challenge for translational research. Some of the gene signatures were discussed from this aspect. Appropriate therapeutic monitoring as well as prediction of treatment efficacies is of great importance for individualization of the treatment. Circulating tumor cells and endothelial cells are promising approach for therapeutic monitoring. Cell death products from cancer cells were also discussed as monitoring marker in patients' sera. In order to promote translational research, collection and storage of high-quality clinical samples are essential. We discussed the system of sample collection and storage at present and in the future in the OOTR institute.
Dr. Chow introduced some ideas about new trials. They include a combination therapy of a molecular target drug and chemotherapy. A combination of a molecular target drug and a hormonal therapy was also discussed. (Summarized by Dr. Takayuki Ueno, Senior Investigator of OOTR)
OOTR Investigators and observers
