Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist

Background. A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients. Methods. Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa. Results. Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone. Conclusion. These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels. Received: July 25, 2000 / Accepted: October 16, 2000     

Epstein-Barr virus nuclear antigen-1-dependent and -independent oriP-binding cellular proteins.

OBJECTIVE: Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and the replication origin, oriP, are essential for the replication and maintenance of latent EBV DNA in cells, but no enzymatic activity has been associated with EBNA-1 protein alone. In this study, we have searched for host cellular proteins that interact with EBNA-1 protein in various B cell lines latently infected with EBV, including a recently EBV growth-transformed cell line. METHODS: By using gel shift analysis, we investigated the interactions of an oligonucleotide containing a single EBNA-1 recognition site, derived from the family of repeats (FR) element of oriP, with protein from cell extracts. RESULTS: The FR oligonucleotide bound a (72-kD) cellular protein in the absence of EBNA-1 and without induction of the previously reported 'anti-EBNA-1 proteins'. The FR oligonucleotide formed complexes with additional proteins from EBNA-1-synthesizing cell lines; these complexes were abolished or supershifted by anti-EBNA-1 monoclonal antibodies. SDS-PAGE analyses of 35S-Met-labeled proteins that bound to a biotin- conjugated FR oligonucleotide, fractionated by a glycerol gradient centrifugation and affinity-purified with streptavidin, showed three major bands, a 72-kD protein, the FR binding of which seemed to be independent of EBNA-1, a 64-kD protein in both EBNA-1-transfected and latently EBV-infected cell lines, and a 45-kD protein in EBV-infected cell lines, which was most prominent in a recently EBV growth-transformed cell line. CONCLUSIONS: The FR element forms complexes with cellular proteins in the absence and presence of EBNA-1. These 72-, 64- and 45-kD cellular proteins might be involved in the function of the oriP and EBNA-1 system.     

Light conditions during sleep period and sleep-related lifestyle in Japanese students.

The effects of light conditions during night sleep on sleep habits and morning-evening preference were studied in Japanese students (18-28 years old). Students who usually used fluorescent or non-fluorescent light on the room ceiling, wall or desk preferred to have a daytime nap significantly later (Mean: 14:50 h) than those who used no light (13:34 h). Students who used no curtain or a half-transparent lace-curtain showed shorter sleep latency (duration from going-to-bed to sleep-onset) than those who used a curtain which shuts off lights from outside. Light conditions during the middle of night and early in the morning may affect the timing of sleep in Japanese students based on the circadian system.     

Phase I study of docetaxel and cisplatin for patients with previously untreated metastatic non-small-cell lung cancer: a Japanese cooperative study

Background. Docetaxel is one of the most active agents used in the treatment of advanced non-small-cell lung cancer. This phase I study was performed to determine the toxicities, maximum tolerated dose, and pharmacokinetics of the combination of docetaxel and cisplatin in patients with non-small-cell lung cancer, and to recommend a dose for phase II study. Methods. Patients were required to have previously untreated metastatic non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 2 or less, be aged between 15 and 74 years, to have a measurable lesion, and to have adequate organ function. Treatment consisted of 1-h infusion of docetaxel on day 1, followed by 2-h infusion of cisplatin (3 h after docetaxel) at the following docetaxel/cisplatin (mg/m²) dose levels: 50/50, 60/50, 60/60, 60/70, and 60/80. At least three patients were accrued at each dose level. Treatment was repeated every 3 to 4 weeks for responders. Administration of granulocyte-colony stimulating factor was permitted when leukocytopenia or neutropenia of grade 3 or more occurred. Results. Of the 29 patients entered, all were assessable for toxicity and response, but 2 were excluded from analyses of dose-limiting toxicity and maximum tolerated dose. Neutropenia (grade 4, for 3 days or more; n = 1), hepatic dysfunction (grade 3 or more; n = 2) and renal dysfunction (grade 2 or more; n = 3) were observed as dose-limiting toxicities. However, the maximum tolerated dose was not detected, even at the highest dose examined. Tumor response occurred in 13 of the 29 patients (45%; 95% confidence interval; 26%–64%). The pharmacokinetic profiles of docetaxel and cisplatin (n = 17) were similar to those observed after the administration of each dose as a single agent. Conclusion. Docetaxel/cisplatin doses of 60/80 mg/m² were recommended for phase II study, because grade 4 neutropenia occurred in 50% or more patients at docetaxel/cisplatin dose levels of 60/60 mg/m² and above, and the doses of these drugs were restricted to within the approved dose ranges for single-agent use in Japan. The responses observed in this phase I study suggest a high degree of activity of this combination against previously untreated advanced non-small-cell lung cancer and warrant a phase II study at the recommended dose level. Received: February 29, 2000 / Accepted: June 22, 2000     

Decreased production of immunoglobulin M and A in autoimmune pancreatitis

Background  

Autoimmune pancreatitis (AIP) is a rare type of chronic pancreatitis caused by an autoimmune abnormality. It is well known that high serum concentrations of IgG4 are helpful for making a diagnosis of AIP; however, it is unclear whether there are abnormalities in the production of other immunoglobulins in AIP.     

Active and Passive Cutaneous Anaphylaxis in Wbb6f1 Mouse, A Mast Cell-Deficient Strain

WBB6F₁ mouse, a mast cell-deficient strain, was tested for active and passive cutaneous anaphylactic reactions. Active cutaneous anaphylaxis was not produced in mice which had been immunized for 1 to 2 weeks by an intraperitoneal injection of bovine serum albumin with either adjuvant, Freund's complete adjuvant or Bordetella pertussis organisms, even though circulatory IgE and IgG₁ antibodies were raised. Passive cutaneous anaphylaxis (PCA) was also absent, when the mice had been sensitized with allogeneic IgE or IgG₁ monoclonal antibodies. However, obvious PCA was produced when allogeneic or xenogeneic hyperimmune serum was employed. These findings indicate that mast cells are not necessarily needed for the production of PCA. Some mechanism quite different from the well-elucidated mechanism, i.e., IgE-or IgG₁ antibody-triggered histamine release from mast cells, seems to be operative.