Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients with advanced adenocarcinoma of the pancreas

BACKGROUND: In advanced adenocarcinoma of the pancreas treatment with 5-fluorouracil (5-FU) or ifosfamide results in response rates of approximately 20%. Continuous infusion of these drugs is on many grounds theoretically attractive and may therefore offer advantages over bolus or short-term infusion. PATIENTS AND METHODS: Sixteen patients with advanced adenocarcinoma of the pancreas with progressive measurable disease and no previous chemotherapy entered the study. After implantation of a subcutaneous infusion chamber patients were treated on days 1-12 with ifosfamide (1.0 g/m2/day) and 5-FU (300 mg/m2/day) as a continuous intravenous infusion using a portable infusion pump. Mesna (1.0 g/m2/day) was added as uroprotective agent from day 1-14. Courses were repeated every 4 weeks. RESULTS: Fifteen of the 16 patients were evaluable for response. One partial response was observed (response rate 7% [95% CI: 0%-32%]). Toxicity occurred in 64% of the courses. Dose limiting toxic effects were grade 3 nausea/vomiting (WHO) in 3 patients, grade 2 mucositis in 1 patient and grade 4 leukopenia in 1 patient. CONCLUSION: Intermittent continuous infusion with ifosfamide, mesna and 5-FU is feasible on an outpatient basis. Although continuous infusion of ifosfamide may have a more favorable toxicity profile, the combination of 5-FU and ifosfamide in this schedule is no more effective than bolus or short-term infusio

Mitogen and antigen induced B and T cell responses of peripheral blood mononuclear cells from the harbour seal (Phoca vitulina)

In vitro assays were developed for studies concerning the functioning of the immune system of the harbour seal (Phoca vitulina). Proliferative responses of peripheral blood mononuclear cells (PBMC) were measured after stimulation with different concentrations of the mitogens concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA) or lipopolysaccharide from Salmonella typhimurium (LPS). Con A and PWM induced strong proliferative responses, while PHA and LPS induced comparatively low proliferative responses. Responses of mitogen stimulated PBMC to recombinant human interleukin-2 (rhIL-2) and in vitro immunoglobulin production by mitogen stimulated PBMC were measured to discriminate between stimulation of T cells and B cells. It was found that Con A and PHA stimulate phocine T cells, PWM stimulates both T cells and B cells and LPS predominantly stimulates phocine B cells. Antigen-specific immune responses were measured after immunization of seals with an inactivated rabies vaccine and/or with tetanus toxoid. Antigen-specific proliferation of PBMC and the presence of antigen-specific antibody forming cells were demonstrated for both antigens in the PBMC of immunized animals. The responses measured in vitro correlated well with the development of specific serum antibody titers to these antigens

Factorization of RSA-140 Using the Number Field Sieve

On February 2, 1999, we completed the factorization of the 140--digit number RSA--140 with the help of the Number Field Sieve factoring method (NFS). This is a new general factoring record. The previous record was established on April 10, 1996 by the factorization of the 130--digit number RSA--130, also with the help of NFS. The amount of computing time spent on RSA--140 was roughly twice that needed for RSA--130, about half of what could be expected from a straightforward extrapolation of the computing time spent on factoring RSA--130. The speed-up can be attributed to a new polynomial selection method for NFS which will be sketched in this paper

Factorization of RSA-140 using the Number Field Sieve

Colloque avec actes sans comité de lecture.International audienceOn February 2, 1999, we completed the factorization of the 140--digit number RSA--140 with the help of the Number Field Sieve factoring method (NFS). This is a new general factoring record. The previous record was established on April 10, 1996 by the factorization of the 130--digit number RSA--130, also with the help of NFS. The amount of computing time spent on RSA--140 was roughly twice that needed for RSA--130, about half of what could be expected from a straightforward extrapolation of the computing time spent on factoring RSA--130. The speed-up can be attributed to a new polynomial selection method for NFS which will be sketched in this paper. The implications of the new polynomial selection method for factoring a 512--bit RSA modulus are discussed and it is concluded that 512--bit (= 155--digit) RSA moduli are easily and realistically within reach of factoring efforts similar to the one presented here

Strategies in filtering in the number field sieve

textabstractA critical step when factoring large integers by the Number Field Sieve consists of finding dependencies in a huge sparse matrix over the field GF(2), using a Block Lanczos algorithm. Both size and weight (the number of non-zero elements) of the matrix critically affect the running time of Block Lanczos. In order to keep size and weight small the relations coming out of the siever do not flow directly into the matrix, but are filtered first in order to reduce the matrix size. This paper discusses several possible filter strategies and their use in the recent record factorizations of RSA-140, R211 and RSA-155

Factorization of a 512-bit RSA Modulus

Colloque avec actes et comité de lecture. internationale.International audienceOn August 22, 1999, we completed the factorization of the 512--bit 155--digit number RSA--155 with the help of the Number Field Sieve factoring method (NFS). This is a new record for factoring general numbers. Moreover, 512--bit RSA keys are frequently used for the protection of electronic commerce---at least outside the USA---so this factorization represents a breakthrough in research on RSA--based systems. The previous record, factoring the 140--digit number RSA--140, was established on February 2, 1999, also with the help of NFS, by a subset of the team which factored RSA--155. The amount of computing time spent on RSA--155 was about 8400 MIPS years, roughly four times that needed for RSA--140; this is about half of what could be expected from a straightforward extrapolation of the computing time spent on factoring RSA--140 and about a quarter of what would be expected from a straightforward extrapolation from the computing time spent on RSA--130. The speed-up is due to a new polynomial selection method for NFS of Murphy and Montgomery which was applied for the first time to RSA--140 and now, with improvements, to RSA--155

Some Parallel Algorithms for Integer Factorisation

Algorithms for finding the prime factors of large composite numbers are of practical importance because of the widespread use of public key cryptosystems whose security depends on the presumed difficulty of the factorisation problem. In recent years the limits of the best integer factorisation algorithms have been extended greatly, due in part to Moore's law and in part to algorithmic improvements. It is now routine to factor 100-decimal digit numbers, and feasible to factor numbers of 155 decimal digits (512 bits). We describe several integer factorisation algorithms, consider their suitability for implementation on parallel machines, and give examples of their current capabilities