The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Cancer Chemotherapy and Pharmacology - Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of...     

Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy

We investigated the presence of anti-human T-lymphotropic virus type I (HTLV-I) IgM in sera and cerebrospinal fluid from patients with HTLV-I-associated myelopathy (HAM) by Western blot analysis. Analyses of 36 serum samples revealed that most patients (31/36; 86.1%) had anti-HTLV-I IgM, whereas only four of 23 (17.4%) HTLV-I carriers had it. In studies of cerebrospinal fluid, anti-HTLV-I IgM was detected in 24 of 36 (66.7%) HAM patients, whereas none was detected in nine HTLV-I carriers. The differences were statistically significant (p less than 0.01). These results suggest that persistent active replication of HTLV-I occurs in the central nervous system as well as in the peripheral blood of HAM patients, and may contribute to the development of HAM.     

Living domino liver transplantation in an adult with congenital absence of portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the splanchnic venous system. Although CAPV is usually detected in the pediatric age group, our patient was a 35-year-old woman. She had been diagnosed with CAPV in 1996 when she was 27 years old. In 1998, she was placed on hemodialysis due to chronic renal failure. After several episodes of encephalopathy in 2002, liver transplantation (LT) was recommended to her and her family. Since there was no suitable living donor candidate, she was put on the waiting list for a deceased donor liver transplant in Japan. In 2004, her ammonia level increased to around 300 microg/dl, and she went into a coma lasting for three days. After recovering from this event, she underwent a living domino transplantation using a whole liver donated by a familial amyloid polyneuropathy (FAP) patient. Her portal vein, which had drained directly into the inferior vena cava (IVC), was transected together with a cuff of the IVC wall and anastomosed to the graft liver portal vein in an end-to-end fashion. In conclusion, liver transplantation proved to be a safe and effective way to save this patient and improve her quality of life.     

A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid]

A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.     

Synthesis of 4,5-diarylthiazole derivatives as blood platelet aggregation inhibitors

A number of 2-substituted 4,5-diphenylthiazoles were synthesized by the nucleophilic substitution of 2-methylsulfonyl-4,5-diphenylthiazole with various sodium alkoxides, amines, and carbanions of active methylene compounds. 2-Methylsulfonyl-4,5-diphenylthiazole was obtained by the potassium permanganate oxidation of 2-methylthio-4,5-diphenylthiazole in the presence of a phase-transfer catalyst. 2-Ethoxy-4,5-bis(4-methoxyphenyl) thiazole was prepared in a similar manner. 2-Ethynyl-4,5-diphenylthiazoles were synthesized by the palladium catalyst cross-coupling reaction of 2-iodo-4,5-diphenylthiazole with monosubstituted acetylenes. These compounds were tested for inhibitory activity against blood platelet aggregation in vitro. Among them, 2-alkoxy-, and 2-(4-methylpiperazin-1-yl)-4,5-diphenylthiazole were found to have potent inhibitory activity.     

Liver damage by the crown-of-thorns starfish (Acanthaster planci) lethal factor

Upon autopsy of mice injected with the crown-of-thorns starfish (Acanthaster planci) lethal factor, a change in color of the liver, swelling of the gall bladder and jaundice were observed. After administration of the lethal factor into mice, activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), acid phosphatase (ACP) and alkaline phosphatase (ALP) were significantly elevated in serum. Hepatic ALP also increased markedly but hepatic GOT, GPT and ACP showed a tendency to decrease. Activity of hepatic LDH first decreased and then returned to control level. Histopathological studies showed that severe degenerative changes such as enlargement and necrosis of hepatocytes were caused in the mouse liver by the lethal factor. These results strongly suggested that the A. planci lethal factor is a potent hepatotoxin.     

A case of granulocyte-colony stimulating factor producing gastric cancer]

We report a case of granulocyte-colony stimulating factor producing gastric cancer with multiple liver metastases. A 68-year-old woman who complained of epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination revealed a type-2 gastric cancer. The laboratory data at admission indicated leukocytosis (35,900/microl) and a high level of serum granulocyte-colony stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we detected multiple liver metastases, chemotherapy was performed. Granulocyte-colony stimulating factor-producing gastric cancer is relatively rare and we summarize previous reports.     

Clinical results of intraperitoneal hyperthermic perfusion combined with surgery in patients with peritoneal recurrence from gastric cancer

Six patients with peritoneal recurrence after radical operation for gastric cancer were treated by an intraperitoneal hyperthermic perfusion (IPHP) combined with surgery (IPHP group). Immediately after surgery, a 2-hour IPHP was performed, using a perfusate containing 10 micrograms/ml of MMC, warmed at the inflow temperature of 46.5 +/- 1.1 degree C. Within the same period of time, 5 patients with intra-abdominal recurrent gastric cancer (control group) were treated by an intraperitoneal administration of MMC 10 mg combined with surgery. These 11 patients had malignant peritoneal effusion and, although in 3 of the control group, ascitic effusion did re-accumulate rapidly soon after surgery, the 6 patients of IPHP group did not re-accumulate post-hyperthermically. The average survival duration of IPHP group is 13.6 +/- 10. 6 months, whereas that for controls is 3.0 +/- 2.1 months. Again, the survival rate for IPHP group surpassed that for controls at p = 0.012 and p = 0.008, in a generalized Wilcoxon method and Logrank method, respectively. Post-hyperthermically, hypoproteinemia and thrombocytopenia occurred transitorily. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence due to gastric cancer.     

Effects of age on susceptibility of chickens to delayed neurotoxicity due to triphenyl phosphite

Triphenyl phosphite (TPP), which is widely used in the chemical industry, is known to produce delayed neurotoxicity in some experimental animals. The effects of aging on the susceptibility to TPP, its disposition and pharmacokinetics, and its in vitro degradation by liver homogenate were studied in chickens. Chickens aged 60 days or less at administration were not affected, but 10 of 15 chickens aged 90 to 180 days developed ataxia 10 to 12 days after the intravenous injection of TPP (50 mg/kg). TPP clearance from the blood and most of the tissues examined was faster in 45-day-old chickens than in 135-day-old chickens. The biological half-life of TPP in the blood was 23.2 min. in the younger group and 30.5 min. in the older group. In the in vitro experiment, the initial TPP concentration of 1.6 x 10(-5) M fell to less than half this level within 60 min. during incubation with liver homogenates from 45-day-old chickens, whereas with homogenates from 135-day-old chickens the level remained high. These results suggested that the age-specific susceptibility to TPP was related to the differences of the tissue load, which derived in part from differing levels of metabolic activity in the liver.