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Biomedical subjects

G P Murphy

Publications and source records attributed to G P Murphy.

At least 19 recordsLinked to original sources
PubMed1992

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

Adult↗
PubMed1992

Relapsing disease.

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Antigens, Neoplasm↗
PubMed1992

The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The participating institutions of the American Cancer Society National Prostate Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A total of 88 cancers were confirmed pathologically, 93% of which clinically were organ confined. In 324 men (62.3%), a recommendation for biopsy was made based solely on the results of transrectal ultrasonography (TRUS); in 69 patients (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%), on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on cancer detection increased as the serum level increased above 4 ng/ml. The positive predictive values of both the DRE and TRUS were influenced significantly by the presence of an elevated PSA level (P = 0.044 and P less than 0.001, respectively). The results of this ongoing multicenter study support the following statements: (1) the prostate cancer detection rate is influenced by this diagnostic triad and (2) the detection rate of organ-confined disease can be improved substantially by early detection programs.

Aged↗
PubMed1992

Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.

Age Factors↗
PubMed1992

Two mechanisms for growth inhibition by elevated transport of sugar phosphates in Escherichia coli.

The Escherichia coli uhp T gene encodes an active transport system for sugar phosphates. When the uhp T gene was carried on a multicopy plasmid, amplified levels of transport activity occurred, and growth of these strains was inhibited upon the addition of various sugar phosphates. Two different mechanisms for this growth inhibition were distinguished. Exposure to glucose-6-phosphate, fructose-6-phosphate or mannose-6-phosphate, which enter directly into the glycolytic pathway, resulted in cessation of growth and substantial loss of viability. Cell killing was correlated with the production of the toxic metabolite, methylglyoxal. In contrast, addition of 2-deoxyglucose-6-phosphate, galactose-6-phosphate, glucosamine-6-phosphate or arabinose-5-phosphate, which do not directly enter the glycolytic pathway, resulted in growth inhibition without engendering methylglyoxal production or cell death. Inhibition of growth could result from excessive accumulation of organophosphates in the cell or depletion of inorganic phosphate pools as a result of the sugar-P/Pi exchange process catalysed by UhpT. The phosphate-dependent uptake of glycerol-3-phosphate by the GlpT antiporter was strongly inhibited under conditions of elevated sugar-phosphate transport. There are thus two separate toxic effects of elevated sugar-phosphate transport, one of which was lethal and related to increased flux through glycolysis. It is likely that the control of uhpT transcription by catabolite repression exists to limit the level of UhpT transport activity and thereby prevent the toxic events that result from elevated uptake of its substrates.

Bacterial Proteins↗
PubMed1991

The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men.

The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary, multicenter effort to assess the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) assay. By June 1990, 2425 men not previously suspected of having prostate cancer had been examined in ten participating clinical centers according to the project protocol. Three hundred ninety-six men (16.3%) were recommended for biopsy on the basis of TRUS or DRE. An analysis of the results of 330 completed biopsies showed 52 cancers detected by DRE and/or TRUS. Forty-four (84.6%) of the men with cancer had positive TRUS examination results compared with 33 (63.5%) with positive DRE. Five additional cancers were discovered as a result of elevated PSA levels. The overall detection rate was 2.4% and this rate varied by age. The detection rate in men 55 to 60 years of age was 1.3% and this rose to 3.3% in men older than 65 years of age. The estimated sensitivity was significantly greater for TRUS compared with DRE (77.2% versus 57.9%; P less than 0.05). The estimated specificity of DRE was greater than that of TRUS (96.3% versus 89.4%; P less than 0.01). The positive predictive value (PPV) for the tests varied as a function of patient and disease characteristics. The overall PPV was 28.0% for DRE and 15.2% for TRUS. The occurrence of elevated PSA levels significantly increased the PPV of both TRUS and DRE. The majority of cancers detected were at early stages. These preliminary data suggest the feasibility of using these techniques to promote cancer control, but additional data and follow-up are needed to assess the significance of the results.

Age Factors↗
PubMed1991

Lucy Wortham James Basic Research Award. Markers of prostatic carcinoma.

Markers of human prostatic cancer are important diagnostic aids in the management of this most common tumor among US men. A rapidly expanding body of basic and clinical knowledge about the properties and behavior of these unique organ-specific macromolecules bridges the gap between sophisticated immunochemistry and everyday practice. As a consequence, the patient benefits, because greater opportunities for early detection of prostatic cancer provide more freedom in selecting the most effective treatment modalities. Parallel improvement in quantitative assessment of an existing tumor mass allows earlier and more precise monitoring of the positive therapeutic responses and/or disease progression, as well as better overall prognosis. In addition, marker molecules can provide specific targets for antibody-directed therapeutic compounds active against prostatic cancer. This study focused on three such markers: prostatic acid phosphatase, prostate-specific antigen, and a new membrane-associated marker defined by a monoclonal antibody called 7E11-C5. A critical evaluation of clinical usefulness and prospects for future developments are presented.

Acid Phosphatase↗
PubMed1991

Immunoscintigraphy of prostatic cancer: preliminary results with 111In-labeled monoclonal antibody 7E11-C5.3 (CYT-356).

A phase 1 study was conducted with the investigational immunoscintigraphic agent, 111In-CYT-356, a radiolabeled, site-specific immunoconjugate of monoclonal antibody 7E11-C5.3, in 40 patients with prostatic carcinoma and known distant metastases. Each patient received a single intravenous infusion of CYT-356 (dose range, 0.1-5 mg) radiolabeled with approximately 5 mCi of 111In. None of the patients experienced adverse reactions. One patient who received a 5-mg dose developed antibodies to the CYT-356 immunoconjugate. 111In-CYT-356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow-up imaging tests, in one patient. Higher CYT-356 doses may clear the blood pool more slowly. These results suggest that 111In-CYT-356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.

Aged↗
PubMed1990

Prospective new developments in laboratory research and clinical trials in prostatic cancer.

Laboratory research continues to develop new methods supporting clinicians in the management of prostatic cancer. Routine measurements of serum prostate-specific antigen (PSA) levels improve diagnosis, provide insight into tumor burden, and sharpen prognostication. New organ-specific antigenic targets are identified for monoclonal antibody-directed diagnostic and radiotherapeutic reagents. Such new immunospecific conjugates are already under evaluation in clinical trials. Cell culture techniques carry the promise of noninvasive early detection and prognostic evaluation of prostatic malignancy in preclinical stages. Molecular mechanisms responsible for androgen regulation of proliferation and malignancy of prostatic cancer are becoming open for scientific inquiry.

Animals↗
PubMed1989

Prognosis in stage D-1 prostate cancer relative to anatomic sites of nodal metastases. National Prostatic Cancer Treatment Group.

The investigators of the National Prostatic Cancer Treatment Group (NPCTG) have entered 212 patients with surgically confirmed stage D-1 prostate cancer in studies to determine the efficacy of adjuvant therapy after either definitive surgery (Protocol 900) or definitive radiotherapy (Protocol 1000). Follow-up indicates that this group represents 70% of all patients with recurrent disease. Because patients with less than 20% nodal involvement were found to have a statistically significant better progression-free-survival (PFS) than those with greater than 20% nodal involvement, we examined the exact anatomic sites of nodal metastases. The status of obturator, external iliac, internal iliac, and common iliac nodes was compared to PFS and overall survival in 198 patients with D-1 disease in both protocols. Results demonstrate no significant difference in either PFS or overall survival relative to anatomic sites of positive nodes. These data suggest that although minimal pelvic nodal metastasis is consistent with improved PFS, there is no predictable anatomic distribution of disease consonant with that better prognosis.

Antineoplastic Agents↗
PubMed1989

Prostate cancer in blacks: an update from the American College of Surgeons' patterns of care studies.

Data from the American College of Surgeons' prostate cancer surveys covering nearly a decade of experience demonstrate that the problem of prostate cancer is unique among black men in the United States. These data show that the distribution of stage at diagnosis changed across the 10-year interval. The data indicate that there have been improvements in the 5-year survival rates of both black and white patients, but the prostate cancer-specific survival of black patients remains significantly poorer than that of whites.

Black or African American↗
PubMed1989

The current and potential status of screening for prostatic cancer in asymptomatic populations.

The recent development of transrectal ultrasound (TRUS) compared to digital rectal exam (DRE), and associated with the introduction of a new marker, prostatic specific antigen (PSA), is presented and reviewed. Two recent studies of self-referred men not known to be at risk for prostatic cancer are reported, and the encouraging results described. The 10-center National Prostate Cancer Detection Project formed in 1986 is updated. Obviously, more studies of such a nature are needed and should be encouraged to develop further the potential for meaningful earlier detection and management of prostatic cancer in the world's aging male population with a rising prostatic cancer incidence rate.

Aged↗
PubMed1989

Paraneoplastic and serologic syndromes of renal adenocarcinoma.

In renal carcinoma, the inappropriate, unscheduled, or aberrant production of hormones and other serologic markers and the resulting clinical or biochemical syndromes are unique manifestations of this tumor. The elaboration of biologically active factors by renal adenocarcinoma may add a metabolic burden to an already compromised host, and thus affect therapy and prognosis; they should be considered before ascribing symptoms to metastasis or dissemination. Similarly it has been suggested that the elaboration of biologically-inactive peptides and proteins is a very common concomitant of neoplasia and the identification of such factors may facilitate earlier diagnosis and novel therapies in patients with renal carcinoma.

Adenocarcinoma↗
PubMed1988

A comparison of diethylstilbestrol or orchiectomy with buserelin and with methotrexate plus diethylstilbestrol or orchiectomy in newly diagnosed patients with clinical stage D2 cancer of the prostate.

From April 1983 to March 1985, 265 patients with newly diagnosed metastatic prostate cancer were randomized to one of three treatment protocols: (1) diethylstilbestrol (DES) or bilateral orchiectomy, (2) the leutinizing hormone-releasing hormone (LHRH) analog buserelin, or (3) methotrexate plus DES or orchiectomy. In 261 evaluable patients there was no significant difference in survival between the three groups. However, progression-free survival (PFS) was significantly different (P less than 0.0005, log-rank test). Of the possible pairwise comparisons for PFS, two showed significance; buserelin was inferior to DES/orchiectomy (P less than 0.05) and buserelin was inferior to methotrexate plus DES/orchiectomy (P less than 0.0001).

Antineoplastic Combined Chemotherapy Protocols↗