SCANNING ELECTRON MICROSCOPIC STUDIES ON ACUTE INTERSTITIAL PNEUMONITIS

Scanning and transmission electron microscopic studies on two autopsy cases of acute Interstitial pneumonitis caused probably by anticancer agents and intravenous hyperalimentation were reported. SEM revealed clearly the light microscopic findings of acute interstitial pneumonitis; hyaline membrane, Masson body, and glandular metamorphosis. Additionally an organization-process of Masson body and the relationship between Masson body and hyaline membrane were shown by SEM. TEM revealed three kinds of myelin-like lamellate structures in the alveolar exudates of both cases, and they were associated with the lamellar body of the B (type II) alveolar epithelium and the secretory granules of Clara-like cell. The myelin-like lamellate structures might suggest the degree of alveolar damage.     

A case of hepatocellular carcinoma with portal tumor thrombus effectively treated by arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil

A 69-year-old female with unresectable hepatocellular carcinoma was treated with continuous arterial infusion of low-dose cisplatin (10 mg/body/day) and 5-fluorouracil (250 mg/body/day). The regimen was continued for 5 days then discontinued for 2 days, and repeated for 4 weeks. The portal tumor thrombus almost disappeared and HCC was smaller than before chemotherapy. Tumor marker (AFP and PIVKA-II) decreased remarkably. As tumor markers increased again 2 months later, the same regimen chemotherapy was performed once more. The patient was treated with arterial chemotherapy as an outpatient. The present case of hepatocellular carcinoma with portal tumor thrombus was effectively treated by arterial infusion chemotherapy with low dose cisplatin and 5-fluorouracil.     

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

Background

Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC.

Methods

We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity.

Results

PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups.

Conclusion

Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

     

Tumor size ≥50 mm as an Independent Prognostic Factor for Patients with Stage II or III Gastric Cancer After Postoperative S-1 Monotherapy: Analysis of a Multi-institution Dataset

World Journal of Surgery - Little is known about the changes in prognostic factors after adjuvant S-1 monotherapy has become widespread as a standard of care for patients with gastric cancer (GC)...     

The novel and orally active thrombin receptor antagonist E5555 (Atopaxar) inhibits arterial thrombosis without affecting bleeding time in guinea pigs

Thrombin is a powerful agonist for platelets, the action of which is mediated by the thrombin receptor protease-activated receptor-1 (PAR-1). Recently, we discovered that E5555 (1-(3-tert-butyl-4-methoxy-5-morpholinophenyl)-2-(5,6-diethoxy-7-fluoro-1-imino-1,3-dihydro-2H-isoindol-2-yl) ethanone hydrobromide) is a potent thrombin receptor antagonist. We evaluated the anti-platelet and anti-thrombotic effects of E5555. E5555 inhibited the binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP) to PAR-1 with a half maximal inhibitory concentration (IC(50)) value of 0.019μM. E5555 showed potent inhibitory effects on human platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.064 and 0.031μM, respectively, but had no effect on platelet aggregation induced by either ADP or collagen. Similarly, E5555 showed potent and selective inhibitory effects on guinea pig platelet aggregation induced by thrombin and TRAP with IC(50) values of 0.13 and 0.097μM, respectively. The antithrombotic activity of E5555 in vivo was evaluated in a photochemically-induced thrombosis (PIT) model using guinea pigs. Oral administration of E5555 at 30 and 100mg/kg prolonged the time to occlusion by 1.8-fold and 2.4-fold, respectively, compared with controls. Furthermore, E5555 did not prolong bleeding time in guinea pigs at the highest tested dosage of 1000mg/kg. The drug interactions between E5555 and tissue plasminogen activator (tPA) were evaluated. Intravenous administration of 1mg/kg tPA significantly prolonged bleeding time, and its effects were not altered by the oral co-administration of 300mg/kg E5555. These results suggest that E5555 could be a therapeutic option for atherothrombotic disease.