Biomedical subjects

W J Ellis

Publications and source records attributed to W J Ellis.

11 recordsLinked to original sources

PubMed1996

Cell proliferation and apoptosis during prostatic tumor xenograft involution and regrowth after castration.

The biological mechanisms involved in androgen-dependent and -independent prostate cancer growth after castration were analyzed in the LuCaP 23.1 human prostate cancer xenograft model. Athymic mice (n = 82) bearing LuCaP 23.1 xenograft were castrated and tumors were harvested at different time points from day 0 to day 112 post castration. In each group of mice, tumor growth rate (TGR), serum PSA concentration, percentage of tumor cells incorporating bromodeoxyuridine (BUdR index), percentage of apoptotic tumor cells assessed by morphological analysis (apoptotic index), and presence of apoptosis-related DNA "ladder" were analyzed. Castration induced a significant decrease in TGR and serum PSA from day 1 to day 7, and a progressive increase in the 2 parameters from day 14 to day 112, heralding androgen-independent tumor relapse. Meanwhile the BUdR and apoptotic indexes varied as follows after castration: an increase was noted for both at day 3, a significant increase in apoptotic index with a decrease in BUdR index from day 5 to day 14, and a progressive decrease in apoptotic index while BUdR index remained at 50% of the pre-castration value from day 28 to day 112. DNA ladder was present sparsely in tumors grown in non-castrated hosts, universally present in tumors from day 1 to day 28 post castration, and frequent in tumors from day 56 to 112. Castration-induced effects in LuCaP 23.1 tumors were characterized by an increase in number of apoptotic cells and a decrease in proliferative activity. The androgen-independent tumor relapse after castration was associated with a low apoptotic index with no increase in proliferative activity.

Animals↗

PubMed1995

Repeat prostate needle biopsy: who needs it?

The indications for repeat prostate needle biopsy after a transrectal ultrasound guided sextant biopsy are not defined. We examined 100 sextant prostate needle biopsies without a diagnosis of malignancy, which were repeated. Carcinoma was detected in 20 repeat biopsies (20%). Stratification based on initial biopsy result revealed carcinoma in 10 of 69 cases (14.5%) without prostatic intraepithelial neoplasia or atypia, 5 of 17 (29.4%) with atypia, 5 of 5 (100%) with grade II or III prostatic intraepithelial neoplasia and 0 of 9 with grade I prostatic intraepithelial neoplasia. Examination of prostate specific antigen (PSA) levels and PSA velocity did not provide statistically significant stratification, perhaps due to the wide variance in these parameters and the small sample size. We conclude that patients with a diagnosis of glandular atypia, or grade II or III prostatic intraepithelial neoplasia on initial biopsy are at high risk for invasive carcinoma and should undergo repeat prostate needle biopsy. A rapidly increasing serum PSA level or grossly abnormal digital rectal examination may also indicate carcinoma not discovered on initial biopsy.

Biopsy, Needle↗

PubMed1994

The significance of isoechoic prostatic carcinoma.

The diagnosis of prostatic carcinoma is most commonly made today by transrectal ultrasound guided needle biopsy. Often hypoechoic and peripheral zone lesions are the only areas sampled. Recently, we showed that this approach missed a quarter of the cancers that would be detected by a systematic biopsy technique. We term these missed cancers isoechoic carcinomas. We reviewed 1,549 systematic sextant prostate needle biopsies, of which 417 cancers were detected and subdivided into hypoechoic cancers (cancers detected on biopsy of a hypoechoic sector and isoechoic cancers (cancers found only in normal [isoechoic] peripheral zone). We noted in men with only isoechoic cancers that fewer biopsy cores per prostate revealed cancer (mean 1.6 versus 3.0, p < 0.0001) and that these men had lower serum prostate specific antigen levels (mean 14.4 versus 43.7, p < 0.001). The Gleason scores for the isoechoic and hypoechoic cancers were indistinguishable. The pathological staging of hypoechoic and isoechoic cancers was also similar. This study suggests that while isoechoic cancers are generally smaller than hypoechoic cancers, they do not represent low grade clinically insignificant carcinomas. A systematic approach to performing prostate biopsy is recommended.

Biopsy, Needle↗

PubMed1994

Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography.

Three tests are commonly used to diagnose prostate carcinoma to date: serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography. We evaluated these 3 tests in 1,001, 6-sector prostate needle biopsies to rule out prostate carcinoma. Of the biopsies 253 (25.3%) revealed prostate cancer. As a single test, PSA was superior to digital rectal examination or transrectal ultrasonography in predicting cancer in this patient population using difference of proportions tests. Receiver operating characteristic analysis also showed PSA to be the superior test. The combinations of PSA plus transrectal ultrasonography and PSA plus digital rectal examination were superior to digital rectal examination plus transrectal ultrasonography. We found cancer in 35 of 188 patients (18.6%) with intermediate PSA levels of 4.1 to 10.0 ng./ml. and normal or asymmetric nonindurated rectal examinations. Only 5 of 79 patients (6.3%) with a normal digital rectal examination and PSA level of less than 4.0 ng./ml. demonstrated carcinoma on biopsy. Of the 5 patients 4 had annual increases in PSA of 40% or greater. While hypoechoic sectors were more than twice as likely as isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 37.6% of the cancers were found in isoechoic sectors. A strategy of performing biopsy of only hypoechoic sectors would have misdiagnosed 24.6% of the patients with prostate cancer. We conclude that serum PSA is the most accurate of the 3 diagnostic tests evaluated. We also recommend a systematic sextant biopsy technique.

Aged↗

PubMed1994

Prostate cancer.

Prostate carcinoma is a growing concern in our aging society. While the disease often follows a indolent course, it is the second leading cause of cancer-related deaths in males. Prostate cancer screening is promising but remains unproven and controversial. The therapy of prostate cancer has changed little over the past 10 years. The tumor remains refractory to conventional chemotherapeutic agents. True containment of this disease will require novel strategies of diagnosis, biologic assessment, and therapy.

Humans↗

PubMed1993

The inability of prostate specific antigen index to enhance the predictive the value of prostate specific antigen in the diagnosis of prostatic carcinoma.

The prostate specific antigen (PSA) level has become an important but imperfect means of detecting prostatic carcinoma. PSA index (serum PSA normalized to estimated gland volume) has been suggested to improve the performance characteristics of PSA alone. In an attempt to confirm this observation, we compared serum PSA alone to the PSA index in 218 men undergoing systematic random prostatic needle biopsy. Total gland PSA index as well as nontransition zone PSA index were calculated using several constants for the estimated contribution to the serum PSA from the transition zone. The Mann-Whitney nonparametric analysis was performed to account for differences in variances within the data set. For the patient population as a whole, all methods of testing were approximately equivalent in the ability to provide a statistically significant (p < 0.01) stratification between patients with benign and malignant biopsies. In patients with a serum PSA level of 4.1 to 10.0 ng./ml. none of the tests was able to distinguish those with carcinoma from those with a benign biopsy. In men with a normal prostate on digital rectal examination serum PSA was superior to other tests in predicting biopsy results. We conclude that PSA index does not enhance the ability of serum PSA alone to predict the presence of carcinoma.

Aged↗

PubMed1993

PSA in benign prostatic hyperplasia and prostatic intraepithelial neoplasia.

Prostate specific antigen has become an important adjunct to the digital rectal examination in screening for prostate cancer. The clinician should be familiar with interpretation of this test. Many men with BPH have elevated serum PSA concentrations; however, the majority of these men will have other pathologic processes such as occult cancer, PIN, or acute inflammation that may account for the elevations in serum PSA. Certainly, serial increases in serum PSA should increase concern that occult carcinoma is present. Patients with PIN may also have elevated PSA concentrations. When PIN is associated with elevated PSA, a high incidence of invasive carcinoma is noted on subsequent biopsy. Further investigation into the associations will further refine the clinical utility of this powerful tumor marker.

Aged↗

PubMed1992

Flow cytometric analysis of small renal tumors.

Flow cytometric deoxyribonucleic acid (DNA) content analysis was performed on 26 renal tumors 3.0 cm. or less in maximum diameter. We noted DNA aneuploid cell populations in 8 of 25 tumors (32%) evaluable for DNA ploidy status. DNA aneuploid cells comprised 7 to 59% of the cells in those tumors. In comparison, 12 of 25 tumors (48%) larger than 3.0 cm. had aneuploid cell populations. S phase cell populations were significantly increased in the small aneuploid tumors compared with the small diploid tumors (p < 0.001). We believe that these small tumors have the potential to behave aggressively and, therefore, they should be treated no differently than larger renal neoplasms.

Adult↗

PubMed1991

Advanced prostatic carcinoma. Early versus late endocrine therapy.

Since the landmark observations of Huggins and Hodges in 1941, androgen deprivation has been the mainstay of treatment for advanced-stage prostate cancer. Although early, poorly controlled studies suggested enhanced survival with hormonal therapy, this view fell into disfavor as a result of the observations of the first and second VACURG studies. Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation, including a reanalysis of the VACURG data, which suggests a survival advantage for younger patients with stage D disease and high-grade tumors who undergo androgen-ablative therapy at the time of diagnosis. The risk-benefit analysis presented in this review is strongly supportive of early hormonal therapy. Finally, long-term survival of patients with metastatic prostate cancer will require the development of novel treatment strategies effective against androgen-resistant tumor cells and their use in concert with early androgen deprivation.

Androgen Antagonists↗

PubMed1988

Phase I and pharmacokinetic studies with the pentacyclic pyrroloquinone mitoquidone.

Mitoquidone (MTQ) is the first member of a new group of pentacyclic pyrroloquinones developed for clinical evaluation as a potential anticancer agent. MTQ demonstrated good activity in a range of experimental solid tumour models, but was weakly active against standard prescreens such as the P388 murine leukaemia. Bone marrow suppression or other significant toxicity was not observed in preclinical studies. Twenty-seven patients were treated with MTQ given as a 4-h infusion either once every 21 days (150-600 mg/m2), once a week (200 mg/m2 per week), or as 5 daily doses repeated every 28 days (60-180 mg/m2 per day). The major adverse events encountered included nausea and vomiting (in virtually all patients), dyspnoea, tumour-related pain, and thrombocytopenia in several patients with pretreatment bone-marrow impairment. Phase I studies were suspended without a maximum tolerated dose being reached because of formulation difficulties. There were no major responses, although stable disease was observed in a number of patients with gastrointestinal malignancies. Temporary remission of B-symptoms occurred in two patients with lymphoma. The plasma pharmacokinetics of MTQ were investigated using an HPLC assay with fluorescence detection. Linear pharmacokinetics were observed with a terminal plasma half-life of 2.9 +/- 2.1 h (n = 18 doses). The volume of distribution was 3.4 +/- 2.6 l/kg and plasma clearance was 629 +/- 469 ml/min per m2. Several soluble analogues with similar antitumour activity are currently under investigation.

Carcinoma↗

PubMed1985

Effectiveness of complete versus partial androgen withdrawal therapy for the treatment of prostatic cancer as studied in the Dunning R-3327 system of rat prostatic adenocarcinomas.

Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.

Adenocarcinoma↗