A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line.

The matrix metalloproteinases (MMPs) are likely to contribute to tumor cell invasion, metastasis and angiogenesis. Several MMP inhibitors have been developed, recently and their anti-tumor efficacy is being evaluated in clinical trials. FYK-1388 is a novel broad MMP inhibitor which blocks the activity of MMP-1, -2, -3, -7, -9, -13 and -14 (MT-MMP-1). It is especially effective against MMP-2 and -9 more so than other MMP inhibitors such as Marimastat, Ro 32-3555 and D-2163. Here, we investigated the anti-tumor efficacy of FYK-1388 using the human fibrosarcoma cell line HT-1080. These cells produced MMP-2 and -9, which FYK-1388 inhibited at a dose of 10(-8) M. FYK-1388 at 0.2 mg/mouse/day significantly suppressed tumor growth when given by s.c. injection for 22 days, experimental lung metastasis after 5 days s.c. injection and also suppressed tumor-induced angiogenesis in the dorsal air sac assay after 7 days s.c. injection. In the MTT assay, FYK-1388 had no effect on the in vitro growth of HT-1080 cells. These results suggest that FYK-1388 possesses anti-tumor efficacy as a result of inhibiting angiogenesis through the suppression of MMP-2 and -9 activity.

[A case of pharyngolaryngeal edema after posterior occipito-cervical operation].

A 70-year-old female developed respiratory failure due to pharyngolaryngeal edema after posterior occipito-cervical fusion. She had a history of total thyroidectomy with bilateral neck dissection for advanced thyroid cancer associated with multiple lung metastases. However, her general condition was good, and she was not in cachexia. Her pulmonary function test revealed %VC of 54% and %FEV1.0 of 79%. This posterior occipito-cervical fusion was necessary for pain relief. Twenty-four hours after surgery she suddenly showed dyspnea, requiring tracheal intubation, and was supported by mechanical ventilation. The pharyngolaryngeal edema was recognized with bronchoscopy from the lower larynx with arytenoid region to nasal choana. In several days she recovered from pharyngolaryngeal edema and was extubated. She was discharged from ICU after close observation for 24 hours after extubation. She developed respiratory distress again due to difficulty in sputum expectoration, resulting in emergency tracheostomy an the floor at midnight. In this case, pharyngolaryngeal edema may have been caused by disturbance of lymphatic flow due to posterior occipito-cervical fusion in a patient with a past history of bilateral neck dissection. We also reviewed the literature in this report.

[The relationship between postoperative body temperature for 24 hours and central nervous system dysfunction in patients of selective cerebral perfusion].

BACKGROUND: Postischemic hyperthermia is known to exert detrimental effect on neurological outcome even 24 hours after brain ischemia in animal experiments. The purpose of this study is to investigate the effect of postoperative hyperthermia in cardiac surgery. METHODS: We studied consecutive patients in elective or emergency cardiac surgery with selective cerebral perfusion. We recorded body temperature (BT) during 24 postoperative hours and JCS at discharge from ICU. RESULTS: BT was higher in JCS III group than in JCS I and II group (P < 0.05). CONCLUSIONS: The results indicated that postoperative BT was associated with consciousness disturbance in cardiac surgery with selective cerebral perfusion. Significant BT elevation during postoperative 24 hours in ICU may be due to brain injury such as infarction or bleeding during selective cerebral perfusion. Postoperative hyperthermia may accelerate penumbra around infarcted area to necrosis, resulting in deep coma, which may imply a possibility of managing BT for further consciousness recovery.

[Respiratory management in a patient with severe tracheal stenosis caused by compression from the ascending aortic arch aneurysm].

In cases of tracheal compression by a mediastinal mass or aortic aneurysm, muscle relaxant might induce fetal ventilatory failure. It is known to be valuable to keep spontaneous breathing in these cases. A 42-years-old woman complicated with Marfan syndrome had acute respiratory failure due to acute progression of tracheal stenosis caused by compression from the ascending and aortic pseudoaneurysm. After the induction of general anesthesia for video-assisted thoracic surgery (VATS) for high-pneumothorax, she was placed in lateral position. Suddenly it became difficult to ventilate her and her oxygenation saturation declined with bradycardia. We returned her to supine position and then could manage to ventilate her easier. But we could not maintain stable ventilation until her spontaneous breathing appeared. VATS was cancelled and she was brought in to the ICU after extubation. In the ICU she developed respiratory distress again soon and was reintubated under consciousness guided by bronchofiber scope. We managed successfully to keep spontaneous breathing intact under proper sedation by three sedative drugs; propofol, midazolam and morphine for 5 days until the next operation. We realized the importance of maintaining spontaneous breathing under proper sedation in a case of severe tracheal stenosis.