Objective To assess whether a new heat‐killed Mycobacterium vaccae preparation (SRL172), which enhances cell‐mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone‐refractory prostate cancer, can stimulate desirable cytokine changes in these patients and modulate the progression of the disease. Patients and methods Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNγ) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell‐mediated) switch. Results There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNγ and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNγ‐secreting cells remained depressed in nine of 10 patients. Conclusion Two patients with advanced hormone‐refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.
Objective To determine whether the use of serum insubetween these groups. The PSA level and age of the patients diCered significantly between the groups (both lin-like growth factor 1 (IGF-1) levels is more eBcient than serum prostate specific antigen (PSA) levels in P<0.001). There was no correlation between IGF-1 and PSA levels, and even when the age diCerence in predicting prostate cancer in patients undergoing prostatic biopsy.the groups was considered, there was still no significant relationship between IGF-1 levels and the inciPatients and methods The study included 94 consecutive patients who required transrectal ultrasonography dence of prostate cancer. In patients with a PSA level of 4-20 mg/L there was no statistically significant (TRUS)-guided biopsies of their prostate and who had blood samples taken before their biopsies. These diCerence in IGF-1 levels between the groups. Conclusion Serum IGF-1 as a tumour marker does not samples were then analysed for IGF-1 and PSA concentrations. Six prostatic biopsies were taken from each help to predict patients with prostate cancer. PSA level and even age were better predictors of the presence of patient; they were assessed and a diagnosis made of prostate cancer or no malignancy.prostate cancer than were serum IGF-1 levels.
Objective To determine the effects of terazosin on blood pressure and on antihypertensive therapy when used in managing benign prostatic hyperplasia (BPH). Patients and methods Safety data from a large, multinational study were analysed retrospectively. Normotensive and hypertensive patients received escalating dosages of terazosin for 10 weeks and were maintained on 5 or 10 mg daily doses for 16 weeks (single‐blind period). After the initial treatment period, only men having sufficient improvements in International Prostate Symptom Score (≥30%) and in peak flow rate (≥10%) were randomly assigned to continue terazosin or to receive placebo for 24 weeks (double‐blind period). Results In hypertensive patients, terazosin reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the single‐blind period; these clinically significant reductions were maintained in patients receiving terazosin during the double‐blind period. However, in normotensive and controlled hypertensive patients terazosin produced no clinically significant mean changes in SBP or DBP during either study period. Terazosin did not adversely affect patients receiving concomitant antihypertensive medication. Conclusion Terazosin is a safe treatment for BPH in normotensive and hypertensive men, including men who are already taking additional antihypertensive drugs.
The ideal psoralen-ultraviolet A (PUVA) regimen for chronic plaque psoriasis has yet to be established. There are four components to a PUVA regimen: the dose of psoralen, the starting dose of UVA, the frequency of treatment and the incremental UVA dose protocol. Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side-effects and the risk of cutaneous carcinogenesis, believed to be independently related to the cumulative dose of UVA and the total number of treatments. The British Photodermatology Group recommends two twice-weekly PUVA regimens: one starts with 50% of the minimal phototoxic dose (MPD) and uses weekly increments of 40%, 30%, 25%, 20%, 15%, 10% and 5% of the previous dose to a maximum of 14.5 J/cm2; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40%, decreasing to 20% once erythema develops. We undertook a prospective randomized controlled trial comparing these regimens in 85 Irish patients. The clearance rate with the MPD regimen was lower than with the skin type regimen, 67.5% vs. 95% (P < 0.05). The reasons for treatment failure were grade 3 erythema and severe PUVA itch. There was a trend suggesting that patients with skin types I and II, but not skin type III, required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen, although this did not reach statistical significance. Grades 2 or 3 erythema were very common in both treatment groups (52. 5% of the skin type group and 45% of the MPD group). This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50-70% of the MPD (rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II) and when large dose increments are used. We suggest that smaller dose increments should be used in patients with skin types I and II.
Objective To evaluate the potential of heat-killed Results SRL172 was eCective as an adjuvant to autologous whole tumour cell vaccination in the prevention Mycobacterium vaccae (SRL172) as a nonspecific immunostimulant and as an adjuvant to whole tumour cell of MAT-LyLu tumours and the survival benefit was equivalent to that provided when the adjuvant was vaccination in the rat model of prostate cancer. Materials and methods SRL172 was used as a vaccine live-attenuated BCG. SRL172 alone did not reduce tumour take or tumour growth in this model and in the prevention and treatment of subcutaneous tumours in rats. Prevention experiments were conduc-neither strategy was eCective in delaying the growth of established MAT-LyLu tumours. In the Lobund-ted using subcutaneous MAT-LyLu tumours in Copenhagen rats, comparing vaccination with Wistar rat vaccination with autologous whole tumour cells and SRL172 significantly delayed the growth of SRL172 alone, SRL172 plus autologous cells, and bacille Calmette-Guèrin (BCG) plus autologous cells established tumours. Conclusion Mycobacterium vaccae deserves further evalu-before tumour implantation. Treatment experiments were conducted using subcutaneous MAT-LyLu ation as an adjuvant to whole tumour cell vaccination in a phase I clinical trial in patients with prostate tumours in the Copenhagen rat and subcutaneous PAIII tumours in the Lobund-Wistar rat. Tumours cancer. Keywords Prostate cancer, immunotherapy, Myco-were induced by subcutaneous injection with tumour cells. Animals were then vaccinated with autologous bacterium vaccae, vaccine, rat model cells, autologous cells plus SRL172, or SRL172 alone. or by the co-injection of adjuvant [5]. In animal models
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