Sialyl Lewis X-dependent lung colonization of B16 melanoma cells through a selectin-like endothelial receptor distinct from E- or P-selectin

Endothelial carbohydrate binding proteins, E- and P-selectins, are thought to mediate sialyl Lewis A/X-dependent hematogenous cancer metastasis. We tested this hypothesis using sialyl Lewis X-dependent B16 melanoma lung targeting and its inhibition with selectin ligand mimicry peptide, IELLQAR. In E/P-selectin doubly deficient mutant mice, sialyl Lewis X-expressing B16 melanoma cells colonized the lung, and IELLQAR inhibited this colonization. However, tumors grown in E/P-selectin-deficient mice were significantly smaller than those grown in wild-type mice. These results indicate that the IELLQAR peptide receptor expressed in the lung vasculature plays a major role in sialyl Lewis X-dependent cancer cells targeting to the lung.     

Low-dose cisplatin and UFT for hormone refractory prostate cancer

OBJECTIVES: Biochemical modulation (BM) was initially used to enhance the effect of 5-fluorouracil (5-FU) by modulating its pharmacological action with the addition of other drugs. BM with low-dose cisplatin and 5-FU or UFT has been examined in cases of advanced gastric or pancreas cancer and 30 to 40% response rates have been reported. In the present study, the effect of BM on hormone refractory prostate cancer (HRPC) patients was examined. METHODS: BM consisting of 5 mg/body of cisplatin 3 times per week and 300-450 mg of UFT/day was given to 30 HRPC patients (median and range of age: 66 and 52-72, respectively). The ECOG performance status was 0 to 1. Gleason score was 7 in 8 patients, 8 in 10 patients and 9 in 12 patients, respectively. The metastatic site was bone in 29 patients (extent of disease on bone scan [EOD] grade 1: 10, 2: 10, 3: 8, 4: 1), lymph node in 8 and liver in 1. RESULTS: Among the 29 patients assessable for bone metastasis, 5 (17%) obtained marked improvement on bone scan. One was EOD grade 4 (super bone scan) and 4 were EOD grade 1-3. Eight (28%) were stable and 16 (55%) progressed on bone scan. Among 8 patients with lymph node metastasis, 4 (50%) showed partial response and 4 (50%) progression. One patient with liver metastasis showed complete response. Fourteen (47%) out of 30 patients showed a PSA decline of 50% or greater. Their median response duration was 8 months (range; 2 to 44 months). Among the 25 patients assessable for bone pain, 7 (28%) improved, 12 (48%) remained stable and 6 (24%) progressed. A side effect of Grade II anemia was seen in one patient. CONCLUSION: BM is effective in almost half of hormone refractory prostate cancer patients.     

Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.     

The evaluation of meconium disease by distribution of cathepsin D in intestinal ganglion cells

Meconium disease (MD) results in intestinal obstruction in the neonate where tenacious meconium is found in the distal ileum and proximal colon. The obstructive symptoms improve at several days of age after some of the meconium is passed. We observed premature infants with MD who underwent ileostomy for intestinal obstruction due to tenacious meconium. Afterward, meconium was passed well and the clinical symptoms improved. After closing the ileostomy, growth and defecation became normal. The MD in our cases was documented by histologic changes in the maturation of ganglion cells observed at the time of ileostomy creation and closure. For an objective evaluation of the maturation of intestinal ganglion cells (IGC), we attempted to distinguish immature from mature cells by the expression of cathepsin D. We examined the distribution of cathepsin D in IGC in patients with MD to test the hypothesis that ganglion-cell immaturity might be related to MD. In ganglion cells at the time of ileostomy, cathepsin D was detected in the perinuclear cytoplasm (immature staining pattern), while at the time of ileostomy closure it was detected in intense granules throughout the cytoplasm (mature staining pattern). We propose that it would be possible to evaluate the maturation of IGC by the intracellular distribution of cathepsin D in MD and suggest that immaturity of IGC might be the cause of MD. Accepted: 28 June 1999     

Effect of 7-Bromo-5-(2-pyridyl)-3H-l, 4-benzodiazepine-2(1H)-one, Bromazepam (Ro 5–3350), a New Minor Tranquilizer, on Psychoneurosis with Special Reference to the Obsessive-Compulsive Symptoms

Clinical application of a minor tranquilizer bromazepam, 7-Bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine-2(lH)-one (Ro 5–3350) was made on 18 cases of obsessive-compulsive neurosis, 10 of anxiety neurosis, 6 hypochondriasis, 4 hysteria and 3 of phobia of bodily odor.

• 1) In 18 cases of obsessive-compulsive neurosis, bromazepam was found markedly effective in 6, effective in 3, fairly effective in 5, ineffective in 2, and aggravated in 2 cases. The effective cases were those with obsessive thinking and manifest anxiety. In other kind of neurosis, bromazepam was markedly effective in 5 and effective in 2 of 10 anxiety neurotic cases, whereas it was almost ineffective in the cases of hypochondriasis, hysteria and phobia of bodily odor.
• 3) The maximum daily dose of bromazepam was 10 to 20 mg in many cases, and 20 to 30 mg in some other cases. The durg is quick-acting to such an extent that it took 2 to 5 days for its action to become manifest in markedly effective cases.
• 4) Various laboratory tests revealed no appreciable abnormality in most cases where bromazepam was employed. Physical side effects such as slight hypotension, dizziness, and sleepiness were observed in a few cases, and mental side effects such as loquaciousness and restlessness in about 20 cases.
• 5) The target symptoms of bromazepam were suggested to be anxiety, tension, and irritation like previously reported other benzodiazepines. The fact that its action of relieving anxiety and tension and of elevating mood was found to be more potent than those of other benzodiazepines and that it was effective on some obsessive-compulsive neurosis that showed little response to other benzodiazepines, suggested that bromazepam is a potent and characteristic new minor tranquilizer of clinical value.

     

Anti-Manic and Prophylactic Effects of Carbamazepine (Tegretol) on Manic Depressive Psychosis A Preliminary Report

• 1). The anti-manic, anti-depressive and prophylactic effects of carbamazepine (CAZP, Tegretol-Ciba Geigy) on the endogenous mani-depressive psychosis (MDP) were investigated on 50 MDP cases. The dosage of the drug ranged from 200 to 1,200 mg daily (usually 400 to 600 mg).
• 2). The effect of CAZP on 33 manic states was: “markedly effective” seven (23%), “effective” six (19%), “slightly effective” five (16%), “ineffective” 13 (42%), whereas the effect on six depressive states was: “markedly effective” one and “ineffective” five. No definite relationship was found between the kinds of drugs in combination use and the effect of CAZP. No significant difference of the CAZP effect was found in the four patient groups with different age of onset of the illness, nor among the “continuous,”“frequent” and “periodic” type cases.
• 3). The prophylactic effect of CAZP on 27 cases in which the assessment of the effect on the manic episode was possible was: “markedly effective” 13 (48%), “effective” seven (26%) and “ineffective” seven (26%), whereas that for depressive episode was: 12 (45%), two (7%) and 13 (48%), and the result of the general assessment on each patient was 14 (43%), 10 (30%) and nine (27%), respectively. The kinds of drugs in combination use, age of onset and type of course of the illness did not have any influence on the prophylactic effect of CAZP.
• 4). The prophylactic effect on MDP of CAZP did not parallel that of lithium salt, but CAZP may be effective on cases which did not respond to lithium and vice versa.
• 5). Side-effects such as ataxia, dizziness, exanthema, drowsiness and headache were observed in five of the cases, and the CAZP was discontinued in four of them.
• 6). The mechanism of effectiveness of the CAZP on MDP was discussed.

     

A case report of hepatocellular carcinoma (Vp4)--an attempt to reduce residual tumor thrombus using combination therapy (hepatic arterial infusion, hepatic arterial embolization and radiation)

A 57-year-old man was found to have elevated levels of HCC markers during an observation of chronic hepatitis C. Diffused hepatoma was involved in the posterior lobe, and tumor thrombus extended into the main portal vein (Vp4). Posterior segmentectomy and tumor thrombectomy were performed. But, CT scan 45 days after the operation showed an enhancement at the residual tumor thrombus in the posterior branch. The patient received a hepatic arterial infusion of 5-FU, followed by hepatic arterial embolization. Then, we chose radiation therapy to the tumor thrombus. The most recent CT showed no enhancement at the reduced tumor thrombus. There have been almost no reports of treatment for residual portal thrombus. Careful observations are necessary in such patients.     

Transection of the innominate artery for tracheomalacia caused by persistent opisthotonus

Patients with cerebral palsy often develop opisthotonus. The trachea may be pinched between the innominate artery and the cervical spine. This compartmentalized thoracic inlet results in severe tracheomalacia. We successfully released tracheal compression by transection of the innominate artery. In case 1, a 4-year-old girl with cerebral palsy and opisthotonus was admitted due to respiratory distress. Bronchoscopy revealed severe tracheomalacia 2 cm above the carina. An endotracheal stent was placed through a tracheostomy. Two months later, she developed tracheal bleeding and bronchoscopy demonstrated a trachea-innominate artery fistula. Magnetic resonance brain angiography showed the presence of Willis circle, and transection of the innominate artery was justified. This was done through a low cervical skin incision. In case 2, a 6-year-old boy with cerebral palsy and opisthotonus had long-standing respiratory distress. Ventilatory support did not resolve the symptoms. The innominate artery was transected in the same fashion as in the first case. Case 1 has been free from respiratory distress for 4 months and case 2 for 3 years. Our experience suggests that the combination of tracheomalacia, opisthotonus causes severe respiratory distress. Transection of the innominate artery is a useful therapeutic strategy to release airway obstruction in this condition.