Calmodulin antagonists increase the expression of membrane-type-1 matrix metalloproteinase in human uterine cervical fibroblasts.

The treatment of human uterine cervical fibroblasts with concanavalin A (ConA), or a specific calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) or trifluoperazine resulted in accumulation of an active form of matrix metalloproteinase 2 (MMP-2, gelatinase A). In contrast, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), a weaker antagonist of calmodulin, did not modulate the activation of proMMP-2. The activation of proMMP-2 was confirmed by the enhanced activity on gelatin and the conversion of proMMP-2 to a 62-kDa form by zymography and western blotting. The plasma membrane, but not the conditioned medium, of the W-7- or trifluoperazine-treated cells activated proMMP-2; this activation was blocked by membrane-type-1 MMP (MT1-MMP) antibody and EDTA. The plasma membrane from trifluoperazine- or ConA-treated cells contained MT1-MMP and tissue inhibitor of metalloproteinases 2. Both trifluoperazine treatment and ConA treatment increased the steady-state levels of MT1-MMP mRNA and proMMP-2 mRNA. These results, together with our previous observations on the production of proMMP-1 (interstitial procollagenase) and proMMP-3 (prostromelysin 1) [Ito, A., Sato, T., Ojima, Y., Chen, L.-C., Nagase, H. & Mori, Y. (1991) J. Biol. Chem. 266, 13598-13601], suggest that calmodulin negatively regulates the matrix turnover by suppressing the production of a number of proMMPs including proMMP-1, proMMP-3 and MT1-MMP, and the activation of proMMP-2 in human uterine cervical fibroblasts.

[Esophageal bypass operation of a patient with esophageal stenosis and esophago-bronchial fistula due to lung cancer].

Esophageal bypass operation was carried out for a patient with lung cancer who was not able to take oral feeding, due to esophageal stenosis and esophago-bronchial fistula. Stomach was used as a esophageal substitute, through antethoracal route. Abdominal esophago-jejunostomy was performed for drainage of esophago-bronchial fistula. Oral intake of foods was started from 11th postoperative day without major complication. And then, she was permitted to discharge only with a jejunostomal feeding tube. Recently the quality of life is emphasized, even in cases in which curativity of cancer cannot be expected. Surgery in such cases entails many risks and then, special care must be taken to determine the indication and procedure of this operation. In the case herein reported, such attention to detail resulted in survival for over one year.

[Clinical analysis of postoperative recurrent nerve palsy in patients undergoing operation of carcinoma of the thoracic esophagus].

From January 1976 to April 1987, 325 cases of carcinoma of the thoracic esophagus were resected in our department. Among these cases, 25 cases were not included because of direct operative deaths or early hospital deaths, and 300 cases were selected for clinical analysis of postoperative recurrent nerve palsy, which occurred in 75 cases (25.0%). The rate of occurrence of this palsy in the last 6-year period was higher than that in the first 6-year period (34.0% and 15.3%, respectively). It was suggested that the extension of surgical procedures to the cervix and upper mediastinum had contributed to this increase in rate. The sides affected by palsy were as follows: left, 56.0%, right 12.0%, bilateral, 24.0%; unknown, 8.0%. The importance of gentle handling of the left recurrent nerve during operation should be emphasized. The rate of occurrence of palsy in the cases of "Iu" was higher than in cases of "Im" and "Ei" (53.3%, 31.6%, 26.8%, respectively). The rate of occurrence of this palsy was significantly higher in the cases in which cervical anastomosis was performed than in cases in which intrathoracic anastomosis was performed (31.9% and 2.8%, respectively; p less than 0.01). Of the cases complicated by this palsy (Group A), tracheostomy was done in 12.0% of the cases and long-term transnasal tracheal tube cannulation or tube reinsertion done in 29.3%. These rates were significantly higher than the rates for cases who did not develop this palsy (Group B). The rates of occurrence of postoperative pulmonary complications within one month after surgery in Group A and Group B were almost same (24.3% and 21.8%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[Cardiocirculatory disturbances after surgery of carcinoma of the thoracic esophagus].

From 1976 to 1985, 277 cases of carcinoma of the esophagus were resected in the Second Department of Surgery, Tohoku University School of Medicine. Postoperative cardiocirculatory disturbances occurred in 114 cases (41.2%), arrhythmia being the disturbance most frequently observed (86.8%). Low cardiac output syndrome occurred in 8 cases and myocardial infarction occurred in 3 cases. The majority of the cases were treated successfully, but 5 patients died within one month after operation. Causes of death were as follows: myocardial infarction, constrictive pericarditis, cardiac tamponade, non-occlusive mesenteric ischemia and acute cardiac failure. Postoperative arrhythmia occurred mainly up to the third postoperative day. Low cardiac output syndrome occurred just after operation or on the first postoperative day. All cases of myocardial infarction occurred on the first postoperative day. The rate of occurrence of cardiocirculatory disturbances in aged patients (greater than or equal to 70) was significantly higher than other group (less than or equal to 69), (56.7%:38.1%, p less than 0.05). The rate of occurrence of cardiocirculatory disturbances in patients who had a history of hypertension or in patients with abnormal preoperative electrocardiographic findings were relatively higher than those in patients who had no history of hypertension or in patients with no abnormal preoperative electrocardiographic findings. The rate of occurrence of cardiocirculatory disturbances in patients who had undergone total resection of the thoracic esophagus was significantly higher than that in patients who had undergone partial resection of the thoracic esophagus (42.8%:23.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Improvement of treatment of carcinoma of the thoracic esophagus, especially in reference to the transition in postoperative combined therapy].

It has become clear that postoperative combined therapy performed in our department has improved the prognosis of patients with carcinoma of the thoracic esophagus and changed the pattern of recurrence. In cases of postoperative radioimmunochemotherapy (a combination of 4000 rad of irradiation, with administration of 5-Fu and bleomycin, and the prescription of OK-432 and/or PSK after irradiation) was effective in preventing recurrence. In cases of n1(+) and n2(+), such therapy was effective in controlling local recurrence such as cervical and thoracic nodes. However, the 5-year survival rate of this group was 44.3%, indicating a need for more effective postoperative therapy. Thus, new radiochemoimmunotherapy (irradiation 4000R, 15-30mg/m2 x 2 CDDP, 2mg/body x 2 VDS) combined with three kinds of cytokines such as tumor necrosis factor (TNF), interleukin-II (IL-II) and interferon (IFN)-alpha has been applied in cases of n1(+), n2(+). Postoperative aggressive chemotherapies (old protocol, PAM treatment with a combination of Pepleomycin, Adriamycin and Mitomycin: Or new protocol, F.CAV treatment with a combination of 5-Fu, CDDP, Adriamycin and Vindesine) were effective in improving the prognosis of patients with n3(+) and n4(+). The 5-year survival rate improved from 2.7% with other therapies to 20. 5% with this therapy.