Masakazu Ueda

Human Betacellulin, a Member of the EGF Family Dominantly Expressed in Pancreas and Small Intestine, is Fully Active in a Monomeric Form

Betacellulin (BTC) was found to be expressed mainly in human pancreas and small intestine. This finding suggests that BTC possesses some specific function distinguished from the other members of epidermal growth factor (EGF) family. To clarify this function, the released form of human BTC has been expressed in E.coli, purified, and characterized. The recombinant human BTC was produced as an inclusion body. This material was dissolved in guanidine-HCl under reducing conditions, refolded, and purified through sequential liquid chromatography. Purified BTC was electrophoresed under reducing conditions and a molecular size of 18 kDa was determined, which is the supposed size of a dimer of the peptide. However, chemical analysis failed to show a covalently linked dimer. The molecular mass of BTC analyzed by mass spectrometry revealed it to be 9 kDa, which is consistent with theoretical value for a monomer. Recombinant BTC showed growth promoting activity for mouse fibroblasts and rat aortic smooth muscle cells which was equivalent to EGF On the other hand, BTC was found to exhibit a growth inhibitory effect on the cells overexpressing EGF receptor.

Basic Study of Appropriate Knot-Tying Force in the Gastrointestinal Tract for Development of Haptic Surgical Robot

While endoscopic surgery has frequently been performed as minimally invasive surgery in recent years, it is more difficult to perform than open surgery. Our experience with endoscopic surgery using the latest surgical robot daVinci at our hospital has shown that robotic surgery is beneficial in terms of the safe and easy performance of difficult surgical techniques, however, one of its drawbacks use of the robot does not impart a feeling that the surgeon’s hands are touching the tissues, making meticulous procedures rather difficult (Anthony et al., 2004). In ordinary open surgery or endoscopic surgery, surgeons apply knot-tying force spontaneously based on their experience and the feel of the tissues being handled. In robotic surgery, on the other hand, the force exerted is decided on the basis of visual information alone, such as the tautness of the thread and degree of deformation of the tissue. We therefore thought that objective data should be obtained to determine the optimal knottying force to apply when suturing during robotic surgery. To achieve this goal we developed forceps for robotic surgery whose tips have six degrees of freedom ( Matsuhira et al., 2003) and a new system at our hospital that displays information about force at the tip of the forceps measured by a sensor to the surgeons on monitor or via auditory signals. No studies have ever been conducted to investigate the relationship between knot-tying force and the efficiency of wound healing in the operated tissue, or to estimate the optimal knot-tying force for tissues. We thought that knowing the optimal knot-tying force for tissues in terms of the efficiency of wound healing would make it possible to tie knots based on the information concerning the force at the tip of the forceps displayed during robotic surgery, and to provide basic data in vivo for the development of robotic forceps that impart a feeling that the surgeon’s hands are touching the sutures and tissues. The purpose of this study was to estimate the optimal knot-tying force by investigating the relationship between the force applied assessed on the basis of the information displayed on the surgeon’s monitor and the efficiency of wound healing in the gastrointestinal tract in canine models. O pe n A cc es s D at ab as e w w w .ite ch on lin e. co m

New Strategy of Treatment for Esophageal Squamous Cell Carcinoma Using Immunotoxin Which Reacts to Epidermal Growth Factor Receptor

Squamous cell carcinoma is by far the most common neoplasm of the esophagus and the survival rate of its patients is generally low [1]. To treat this cancer more effectively, it is necessary to develop a strategy of targeted cancer therapy. Most squamous carcinoma cells hyperproduce epidermal growth factor (EGF) receptor [2, 3], and EGF in turn promotes the growth of EGF receptor-hyperproducing squamous carcinoma cells in vivo [4]. Moreover, an elevated EGF receptor level is a significant prognostic factor for patients with esophageal squamous cell carcinoma [5]. Therefore, since EGF and its receptor system play an important role in the growth of this cancer, EGF receptor is an ideal cell surface object for targeted therapy. We synthesized an immunotoxin consisting of murine monoclonal antibody (B4G7) against human EGF receptor and gelonin, a 60s ribosome-inactivating protein. We studied the cytotoxic effects of the immunotoxin on squamous carcinoma cells and tumors, and investigated the possibility of it as a new treatment for squamous cell carcinoma.

Clinical Implification of Molecular Biological Parameter for Prognostic Factor in Digestive Organ Cancer.

消化器癌における分子生物学的パラメーターの予後因子としての有用性を明らかにすることを目的として, 癌遺伝子増幅の有無と予後や再発など癌患者の臨床像との関連を解析した.その結果食道癌では, int-2およびc-erb B癌遺伝子増幅が, 胃癌ではint-2およびc-erb B-2癌遺伝子増幅が高率に認められたが, 大腸癌や肝細胞癌では, いずれの癌遺伝子も増幅頻度は10%以下であった.食道癌, 胃癌ではint-2増幅群で術後累積生存率が低下し, さらに食道癌では遠隔臓器転移が, 胃癌では腹膜転移と遠隔臓器転移が非増幅群に比較して有意に高率であった.c-erb B癌遺伝子増幅は食道癌で高率にみられたが, これらの症例ではいずれも手術時にリンパ節転移がみられ, しかも術後5年生存率は低下していた.以上, 分子生物学的手法により癌遺伝子増幅を検索することにより, 癌患者の治療上重要な情報を得ることが可能であり, 有用な腫瘍マーカーであることが明らかにされた.