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Biomedical subjects

R Sharifi

Publications and source records attributed to R Sharifi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia.

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Recently PTHrP has been shown to be an early-response gene that may be involved in cellular proliferation or differentiation. In addition, PTHrP has been implicated in the pathogenesis of bone metastases. Bone metastases are a significant complication in patients with prostate cancer. We compared the expression of PTHrP by immunohistochemical staining using a monoclonal antibody directed against epitope between amino acids [53-64] in benign prostatic hyperplasia (BPH) with that in various stages of prostate cancer. Tissue sections were obtained on formalin-fixed paraffin-embedded blocks from BPH, well-differentiated prostate cancer, poorly differentiated prostate cancer, lymph node metastases (n = 15 each), and normal prostate (n = 2). In the normal prostate tissue there was no staining observed. In BPH, 13 of 15 tissue samples were positive for PTHrP immunoreactivity. An average of 33% of the cells stained positive with 1+ intensity. All samples from prostate cancer stained positive for PTHrP. In the samples from well-differentiated prostate cancer, an average of 87% of cells stained positive for PTHrP, whereas 100% of cells were positive in poorly differentiated and metastatic tumors. The intensity of staining was 3+ in well-differentiated tumors and 4+ in poorly differentiated tumors. Therefore, the expression of PTHrP is enhanced in prostate cancer as compared with BPH and is greater in poorly differentiated carcinoma as compared with the well-differentiated tumors. The role of PTHrP in the pathogenesis of prostate cancer deserves further study.

Adult↗
PubMed1996

Maximal androgen blockade for patients with metastatic prostate cancer: outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study Group.

OBJECTIVES: To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). RESULTS: At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Adult↗
PubMed1996

A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group.

Between January 1992 and September 1993, 813 patients with stage D2 prostate cancer were enrolled in a multicentre, double-blind (for antiandrogen therapy) trial and randomised to antiandrogen therapy with Casodex (bicalutamide, 50 mg once daily) or flutamide (250 mg three times daily) and to luteinising hormone-releasing hormone (LHRH) analogue therapy with Zoladex (goserelin, 3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days). Time to treatment failure was the primary efficacy endpoint. At a median follow-up time of 49 weeks, there was a significant (p = 0.005) difference between groups in time to treatment failure in favour of Casodex plus LHRH analogue. Overall, 168 (42%) of 404 patients in the Casodex plus LHRH analogue group and 218 (53%) of 409 patients in the flutamide plus LHRH analogue group reached a treatment failure endpoint. Although a cause-specific treatment-failure analysis was not performed, the difference between groups in treatment failure attributed to adverse events (mainly diarrhoea) was evident primarily in the first 7 months of therapy. The difference between groups in treatment failure for objective progression was most evident after 1 year of therapy. With further follow-up (median time of 95 weeks), the result for time to treatment failure, although no longer statistically significant, were consistent with the previous finding of an improvement in time to treatment failure associated with Casodex plus LHRH analogue therapy. With a median of 95 weeks of follow-up, 34% of deaths had occurred. The survival analysis was not dissimilar between the 2 groups. At 49 weeks median follow up, the incidence of diarrhoea was significantly (p < 0.001) lower among patients in the Casodex plus LHRH analogue group. Diarrhoea led to withdrawal from therapy for 2 patients in the Casodex plus LHRH analogue group, compared with 25 patients in the flutamide plus LHRH analogue group. In conclusion, Casodex plus LHRH analogue is well tolerated and effective with an improvement in time to treatment failure over flutamide plus LHRH analogue. Survival was not dissimilar between the 2 treatment groups.

Androgen Antagonists↗
PubMed1995

Effects of sex steroids on cell growth and C-myc oncogene expression in LN-CaP and DU-145 prostatic carcinoma cell lines.

The prostate gland is dependent on androgens for the maintenance of its normal growth and functional integrity. Initially, growth of the majority of prostate tumours can be manipulated by endocrine therapy. In the present study, we evaluated the effects of sex steroids on the cell growth and expression of the C-myc oncogene in two human prostatic adenocarcinoma cell lines. We found that dihydrotestosterone increases the proliferation rate of prostatic cells, and amplification of C-myc oncogene is hormone-dependent. We also demonstrated a positive correlation between the number of cells positive for C-myc oncogene and oncoprotein in hormone-treated prostate cell lines.

Adenocarcinoma↗
PubMed1995

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group.

OBJECTIVES: To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). RESULTS: With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.

Adenocarcinoma↗
PubMed1995

Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma.

OBJECTIVES: Single-agent therapy with bicalutamide, a nonsteroidal antiandrogen, was compared with castration, either surgical or medical, in patients with untreated Stage D2 prostate cancer. METHODS: In an open, randomized, multicenter trial, patients were randomized to treatment with 50 mg bicalutamide (n = 243) once daily or to castration (n = 243), either orchiectomy or depot injection of goserelin acetate every 28 days. Primary efficacy endpoints were times to treatment failure and objective disease progression and survival. Assessments included review of measurable metastases, prostate dimensions, Eastern Cooperative Oncology Group performance status, pain, analgesic requirements, and quality of life responses. RESULTS: The median duration of therapy was 39 weeks for bicalutamide-treated patients and 42 weeks for castrated patients; treatment failure occurred in 53% and 42% and disease progression in 43% and 33%, respectively. Treatment effects favored castration for both endpoints (P < or = 0.002), with hazard ratios (bicalutamide:castration) of 1.54 (95% confidence interval [CI], 1.18 to 2.00) for time to treatment failure and 1.6 (95% CI, 1.19 to 2.15) for time to disease progression. From the 1-year survival analysis, the hazard ratio for probability of death was 1.29 (95% CI, 0.96 to 1.72). Thus far, with a median follow-up of 86 weeks, median survival has not been reached in either group. Changes from baseline in several quality of life variables were significantly different (P < or = 0.01) between treatment groups periodically from months 1 to 6, and all favored bicalutamide. Overall, the antiandrogen was well tolerated compared with castration; with bicalutamide, hot flushes occurred less often and breast tenderness and gynecomastia more often. CONCLUSIONS: Although a dosage of 50 mg of bicalutamide once daily was not as effective as castration, the favorable quality of life outcomes and the low incidence of nonhormonal adverse events provide reasons to evaluate bicalutamide, as a single therapeutic agent, at higher doses.

Aged↗
PubMed1995

Ethanolamine sclerotherapy of a renal cyst.

We report the effective use of 5% ethanolamine oleate to sclerose a large simple renal cyst. The comparative advantages of ethanolamine versus other sclerosants are discussed in terms of adverse effects, availability and convenience. Guidelines to optimize sclerotherapy with ethanolamine are provided.

Aged↗
PubMed1995

Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group.

PURPOSE: Nonrandomized clinical trials have suggested that preoperative androgen deprivation can decrease the likelihood of positive surgical margins in patients with clinically localized prostate cancer. A multicenter prospective randomized trial compared radical prostatectomy alone to radical prostatectomy after 3 months of leuprolide acetate depot and flutamide in patients with stage cT2bNxM0 prostate cancer and a serum prostate specific antigen level less than 50 ng./ml. MATERIALS AND METHODS: We randomized 149 patients to undergo androgen deprivation and 138 to undergo lymphadenectomy with (137) or without (1) prostatectomy. Of the 154 patients randomized to the surgery alone group 144 underwent pelvic node dissection with (138) or without (6) prostatectomy. RESULTS: There was no statistically significant difference between the 2 groups in operating time, blood loss, need for transfusion, postoperative morbidity or length of hospital stay. There were 4 rectal and 2 ureteral injuries in the surgery alone group and none in the pretreatment group (p < 0.05). Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47% versus 78%, p < 0.001), positive surgical margins (18% versus 48%, p < 0.001) and tumor at the urethral margin (6% versus 17%, p < 0.01). CONCLUSIONS: Long-term followup data will be needed to determine whether there will be a lower incidence of biochemical relapse as determined by prostate specific antigen, local recurrence or metastasis, with an improvement in patient survival.

Aged↗
PubMed1995

Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism.

Treatment of priapism with intracavernous alpha-adrenergic agonist vasoconstrictor agents is well accepted, particularly for patients with priapism secondary to intracavernous injections of papaverine, phentolamine and/or prostaglandin E1. Although many alpha-adrenergic agonists are commercially available, phenylephrine is preferred because it has potent and selective alpha 1-adrenergic stimulatory properties, which can decrease arteriolar flow to the cavernous sinusoids, and no beta 1-stimulatory effect, which could cause arrhythmias and angina in susceptible patients. Before intracavernous injection or irrigation an alpha-adrenergic agonist must be diluted. However, no readily available reference source lists this information. Therefore, we prepared a chart for extemporaneous preparation of dilutions of alpha-adrenergic agonists for intermittent injection or irrigation.

Adrenergic alpha-Agonists↗
PubMed1991

Bone scan as a stratification variable in advanced prostate cancer.

The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.

Aged↗
PubMed1991

Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse after the use of at least one other standard anti-cancer agent. The patient was to have received no prior radiotherapy or intravesical therapy for at least 4 weeks prior to entry. Patients also did not suffer significant cardiac dysfunction, such as angina, congestive heart failure, or uncompensated cardiomyopathy. All patients were given 4-6 doses of intravesical novantrone at the same dose level at weekly dosing interval. Patients were required to retain the drugs in the bladder for 2 h. Baseline study included history/physical, hematology, blood chemistry, cystoscopy, bladder barbotage, urine cytology, cystometrogram to assess the bladder capacity, and finally, chest X-ray, EKG, and MUGA scan, if indicated. Weekly assessment involved toxicity notation, blood chemistry, hematology and urinalysis. Monthly assessment included physical examination, toxicity notation, hematology, urinalysis and blood chemistry. Within 4 weeks of completion of the last dose, patients underwent repeat cystoscopy to assess disease status. Patients who responded to the 4-6 week induction phase were entered in a monthly dose regimen for up to 5 months. A total of 23 patients were enrolled: 22 males and 1 female. One patient dropped out before receiving medication because of a protocol violation for entry criteria. Twenty-two patients were eligible for assessment of safety and 20 were eligible for assessment of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. The Leuprolide Study Group.

In a phase III, open, multicenter study we evaluated the safety and efficacy of the depot formulation of leuprolide (7.5 mg. injected intramuscularly every 4 weeks) in patients with stage D2 prostate cancer who had not previously received systemic treatment. Serum testosterone, luteinizing hormone and plasma leuprolide levels were monitored during the 24-week study period. Median interval to onset of castrate testosterone levels was 21 days and mean testosterone levels decreased to within the castrate range by week 3 of treatment. After onset of castrate levels there were no escapes (defined as 2 consecutive values of greater than 50 ng./dl.) of testosterone levels during the 24 weeks. Suppression of testosterone did not differ significantly from that observed in patients receiving the daily subcutaneous injection of leuprolide acetate in the first 24 weeks of another study. Objective response (no progression) to treatment occurred in 81% of 53 evaluable patients and adverse (related and unrelated) events were reported in 45 of the 56 patients. The response rate and incidence of adverse events in this study did not differ significantly from those occurring with the daily formulation. We conclude that the depot formulation of leuprolide is safe and effective in the treatment of advanced prostatic cancer, and that the safety and efficacy of this formulation do not differ significantly from those of the daily subcutaneous formulation.

Aged↗
PubMed1990

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate.

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

Clinical Trials as Topic↗
PubMed1990

Oxybutynin-induced reflux esophagitis.

Oxybutynin has less anticholinergic activity than propantheline bromide. Therefore, oxybutynin is often preferentially prescribed for patients at risk of morbid complications of atropine-like adverse effects. We report a case of oxybutynin-induced reflux esophagitis. This probably resulted from the anticholinergic action of oxybutynin, which decreased lower esophageal sphincter tone. We outline a management approach for patients who experience this adverse effect due to oxybutynin or other commonly prescribed medications.

Adult↗
PubMed1990

Causes, presentation and survival of fifty-seven patients with necrotizing fasciitis of the male genitalia.

This analysis of our experience with 57 men with necrotizing fasciitis of the genitalia was done to identify prognostic variables and to assess the results of a treatment policy of immediate and, if required, repetitive surgical debridements. The mean age of the patients was 55 years. Thirty-eight patients were alcoholics or diabetics, or both. All of the infections were of a genitourinary, anorectal or cutaneous source. Thirty-five per cent of the infections were confined to the genitalia and 65 per cent extended to the abdominal wall or thigh, or both. Forty-seven patients survived. Survival was associated significantly with a younger age, a serum blood urea nitrogen (BUN) level of less than 50 milligrams per deciliter at presentation, the absence of a constellation of abnormalities at presentation consistent with sepsis and a decreased incidence of major complications after initial débridement (p less than 0.05 to 0.01). Survival was not associated with the extent of infection, the duration of symptoms before hospitalization, systemic risk factors, the source of infection, abnormal findings at presentation (excluding a BUN of greater than 50 milligrams per deciliter) and the bacteriologic factors of the infection. Both localized and extensive necrotizing fasciitis of the male genitalia are potentially lethal disorders that require prompt treatment.

Bacterial Infections↗