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G P Murphy

Publications and source records attributed to G P Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1999

'Green revolution' genes encode mutant gibberellin response modulators.

World wheat grain yields increased substantially in the 1960s and 1970s because farmers rapidly adopted the new varieties and cultivation methods of the so-called 'green revolution'. The new varieties are shorter, increase grain yield at the expense of straw biomass, and are more resistant to damage by wind and rain. These wheats are short because they respond abnormally to the plant growth hormone gibberellin. This reduced response to gibberellin is conferred by mutant dwarfing alleles at one of two Reduced height-1 (Rht-B1 and Rht-D1) loci. Here we show that Rht-B1/Rht-D1 and maize dwarf-8 (d8) are orthologues of the Arabidopsis Gibberellin Insensitive (GAI) gene. These genes encode proteins that resemble nuclear transcription factors and contain an SH2-like domain, indicating that phosphotyrosine may participate in gibberellin signalling. Six different orthologous dwarfing mutant alleles encode proteins that are altered in a conserved amino-terminal gibberellin signalling domain. Transgenic rice plants containing a mutant GAI allele give reduced responses to gibberellin and are dwarfed, indicating that mutant GAI orthologues could be used to increase yield in a wide range of crop species.

Alleles↗
PubMed1999

Follow-up evaluation of a phase II prostate cancer vaccine trial.

BACKGROUND: A phase II trial, involving infusions of autologous dendritic cells (DC) and two human histocompatibility antigen (HLA-A2)-specific prostate-specific membrane antigen (PSMA) peptides, was recently completed. Thirty percent of the participants, including subjects with hormone-refractory metastastic disease, and those with suspected local recurrence of prostate cancer, were identified as clinical responders. This report describes the follow-up evaluation of 19 responders in the two study groups. METHODS: After conclusion of the study, study participants were subjected to follow-up evaluations at 6-8-week intervals. Each responder was reevaluated for response status, and duration of response was determined. RESULTS: Subjects were observed for an average of 291 days (metastastic group, group A-2) and 557 days (local recurrence group, group B), which included the treatment and follow-up periods. The average duration of response was 149 days for group A-2, and 187 days for group B. A majority of responders (11/19; 58%) were still responsive at the end of the current follow-up. CONCLUSIONS: The responses observed may be significant and relatively durable. This study suggests that DC-based cancer vaccines in the future may provide an additional therapy for advanced prostate cancer.

Antigens, Surface↗
PubMed1999

GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial.

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; Leukine [sargramostim], Immunex Corp., Seattle, WA) was administered to a subgroup of 44 patients in a phase II clinical trial for prostate cancer using DC pulsed with HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides. Our purpose was to determine if GM-CSF caused any enhancement of patients' immune responses, including enhancement of clinical response to the DC-peptide treatment. This report compares the clinical responses to DC-peptide infusions with and without systemic GM-CSF treatment. METHODS: GM-CSF was administered by subcutaneous injection at a dose of 75 microg/m2/day for 7 days with each of six infusion cycles. Prefilled syringes were supplied to the patients for self-administration. RESULTS: One complete and 8 partial responders were identified among 44 patients who received GM-CSF, as compared to 2 complete and 17 partial responders among 51 patients who did not receive GM-CSF. For patients who received GM-CSF and were tested by delayed-type hypersensitivity (DTH) skin test, 3 cases of improved immune response were identified, compared to 5 cases of improvement in patients who did not receive GM-CSF. The main GM-CSF side effects reported were local reactions at the site of injection, fatigue, pain, and fever. Most reported side effects were of mild severity, with some cases of moderate severity leading to discontinuation of GM-CSF. CONCLUSIONS: Our results suggest GM-CSF as employed in this trial did not detectably enhance clinical response to DC-peptide infusions, or significantly enhance the measured immune response.

Adjuvants, Immunologic↗
PubMed1999

Association of free PSA percent, total PSA, age, and gland volume in the detection of prostate cancer.

BACKGROUND: Measurement of the free fraction of total prostate-specific antigen (fPSA%) has been proposed as a useful addition to total PSA for the detection of prostate cancer. METHODS: We assessed the performance of fPSA% in differentiating men with prostate cancer from men without cancer in a group of 1,709 subjects studied in five institutions. RESULTS: On the basis of PSA testing, digital rectal examination, and ultrasound examination conducted at one or more visits, 229 cancers were diagnosed. The mean fPSA% in men with cancer was 9.1% compared to 18.9% in men without cancer. The fPSA% varied by age, with men under 60 having a mean fPSA of 13.9% compared to 17.5% in men 60-69 years old and 19.8% in men over age 70. Significant associations of fPSA% with gland volume and PSA level were also observed. The sensitivity, specificity, and positive predictive value of different fPSA% cutoff levels were assessed in 513 men who underwent sextant biopsy. Sensitivity of 85.4%, 32.1% specificity, and a 39.2% positive predictive value were observed using an fPSA cutoff of 15% in men with PSA in the 4.0-9.9 ng/ml range. Sensitivity of 96.9%, 12.3% specificity, and a 36.2% positive predictive value were observed using an fPSA cutoff of 20% in the same men. If 15% fPSA had been used as a biopsy criterion in men with PSA of 4.0-9.9 ng/ml, the number of biopsies performed could have been reduced by 21.2%, with a concomitant reduction in cancer detection of 14.6%. Using a 20% fPSA criterion, biopsies would have been reduced 12.7%, with a 3.1% reduction in cancer detection. CONCLUSIONS: These results provide some evidence that the detection of prostate cancer is enhanced by measuring fPSA% in addition to the established measure of total PSA level. Further research is needed to identify other markers that have better sensitivity and specificity.

Adult↗
PubMed1999

Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment.

BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 and -P2). This report describes the evaluation of 37 subjects admitted with presumed local recurrence of prostate cancer after primary treatment failure. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at 6-week intervals. Clinical monitoring was conducted pre-, during, and post-phase II study. Data included: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, and chest X-ray, as well as other assays to monitor cellular and humoral immune responses. RESULTS: One complete and 10 partial responders were identified from this group based on National Prostate Cancer Project criteria, or on a 50% reduction of prostate-specific antigen (PSA), or on a significant resolution in lesions (biopsy-proven when possible) on ProstaScint scan. CONCLUSIONS: About 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggests that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose primary treatment failed.

Aged↗
PubMed1999

Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease.

BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific PSMA peptides (PSM-P1 and -P2). This report describes thirty three subjects with hormone-refractory metastatic prostate cancer without prior vaccine therapy history who were evaluated and reported as a group. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at six week intervals. Clinical monitoring was conducted pre-, during, and post- phase II study. Data collected include: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, chest x-ray, as well as assays to monitor cellular immune responses. RESULTS: Six partial and two complete responders were identified in the phase II study based on NPCP criteria, plus 50% reduction of prostate-specific antigen (PSA), or resolution in previously measurable lesions on ProstaScint scan. CONCLUSIONS: Over 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggested that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose disease no longer responds to hormone therapy.

Adult↗
PubMed1999

Review of phase II hormone refractory prostate cancer trials.

In men with hormone refractory metastatic prostate cancer, single agents have demonstrated an objective response when using a response rate greater than standard treatment in prior National Prostate Cancer Project (NPCP) trials. Among these agents are methotrexate, cisplatin, 5-fluorouracil, cyclophosphamide, doxorubicin, estramustine, methyl N-(2-chloroethyl)-N'-cyclohexyl-Nnitrosourea (CCNU), 5-(3,3-dimethyl1-triazenyl)1H-imidazole-4-carboxamide (DTIC), and vinblastine. Other combinations of protocols have been previously evaluated. Currently under review is a 1 4-year follow-up on an adjuvant trial (NPCP 900/1000) where all patients had a bilateral pelvic lymphadenectomy. These patients were then randomized to surgery or radiation, and received either cyclophosphamide, estramustine, or no therapy for 2 years. Clinical results showed there was no difference in disease-free survival or survival rates between those patients in the group who had T3 prostate cancer, and those with negative pelvic lymph node dissection. The drugs diethylstilbestrol, megestrol, or streptozocin have been used. In clinical trials, the single agent diethylstilbestrol usually had a better effect. Combinations of estramustine with vinblastine were also effective when compared with the results of standard treatment. When comparing patients who relapsed from hormone refractory prostate cancer, there was no significant statistical response rate difference (P = <0.05) in patients who were offered either flutamide or estramustine. To determine more accurately the positive results from these trials, the pre-prostate-specific antigen (PSA) era of stable disease must be re-evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Vaccine therapy for prostate cancer.

Vaccine therapy may provide an alternative for prostate cancer patients whose disease no longer responds to hormone therapy. Administration of dendritic cells pulsed with prostate-specific membrane antigen (PSMA) induces cellular immune responses against the tumor with virtually no adverse effects. About 30% of the evaluable patients were identified as partial responders, based on the National Prostate Cancer Project (NPCP) criteria. In addition, there was a 50% decrease of serum prostate-specific antigen or resolution of previously measurable lesions on imaging. Dendritic cell vaccine therapy may have a synergistic effect, when combined with other therapies.

Cancer Vaccines↗
PubMed1999

Expression and purification of prostate-specific membrane antigen in the baculovirus expression system and recognition by prostate-specific membrane antigen-specific T cells.

Antigen-specific immunotherapy of cancer depends on a consistent source of well-defined protein antigen. Production of recombinant protein offers the obvious solution to this problem but few comparisons of recombinant and native proteins in cellular immune assays have been reported. We report expression of a putative immunotherapy antigen, prostate-specific membrane antigen (PSMA), in insect cells using a baculovirus vector. T cells stimulated with recombinant PSMA or native PSMA derived from the LNCaP cell line recognized both native PSMA and recombinant, baculoviral PSMA. These data indicate that PSMA produced in Sf9 cells is immunologically cross-reactive with native PSMA and therefore suitable for immunotherapy as it is recognized by both cellular and humoral immune responses.

Antibody Formation↗
PubMed1998

Regional diversity and breadth of the National Cancer Data Base.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. This article describes the most current (1995) data. METHODS: Since 1989, 7 calls for data have been issued, yielding a total of 5,558,389 cancer patient reports for the years 1985-1995. A total of 1849 hospital cancer registries have participated in at least 1 of the calls for data. RESULTS: One thousand one hundred and fourteen hospitals from 50 states and the District of Columbia reported 655,627 cases for the diagnosis year 1995. The hospitals represented a wide range of sizes (187 [16.8%] with 1000+ cases annually, 405 [36.4%] with 500-999 cases annually, 255 [22.9%] with 300-499 cases annually, 211 [18.9%] with 100-299 cases annually, and 56 [5%] with < 100 cases annually) and types (21 [1.9%] National Cancer Institute [NCI]-recognized cancer centers, 119 [10.7%] government hospitals, 102 [9.2%] teaching hospitals, 256 [23.0%] large community hospitals, 297 [26.7%] medium/small community hospitals, and 257 [23.1%] nongovernmental hospitals without approval status from the Commission on Cancer or NCI recognition). Remarkably similar distributions of cases by primary site and age were reported from each of six U.S. geographic regions. In addition, within each of these six regions, the cases were reported from a wide range of income strata and ethnicities. For several states, relatively few cancer cases were reported. For several examples of relatively rare patient and tumor groups, all reported cases between 1985-1995 included potentially useful quantities of patients in whom further study of such special groups was warranted. CONCLUSIONS: The authors conclude that the reported cases most likely are representative at the regional (but not state) level of cancer patients diagnosed and treated at U.S. hospitals with regard to types of cancer and ages of the patients. They conclude further that cancer reporting may be quite diverse within each region with regard to other known patient and reporting institution characteristics.

Databases as Topic↗
PubMed1998

ProstaScint scan may enhance identification of prostate cancer recurrences after prostatectomy, radiation, or hormone therapy: analysis of 136 scans of 100 patients.

BACKGROUND: Primary extraprostatic spread or failure after prostate cancer treatment can occur locally in the prostatic fossa and/or metastasize to regional and/or distant lymphatics and/or in bone. We evaluated the ability of the ProstaScint (Cytogen Corp., Princeton, NJ) scan to identify soft tissue recurrence of prostate cancer in patients who failed primary treatment, and we monitored their responses to a secondary treatment. METHODS: The 111indium-labeled monoclonal antibody (ProstaScint) was evaluated in a series of 136 consecutive scans associated with a complete set of relevant clinical and biochemical data. These scans represented 100 patients, imaged between November 1994-May 1998, who underwent a definitive prostate cancer treatment followed by evidence of recurrence. All patients had serum prostate-specific antigen (PSA), Western-blot serum prostate-specific membrane antigen (PSMA), and bone scans. Prostatic fossa and/or lymph node biopsies were available in 33 patients. RESULTS: Overall, no adverse reactions were related to any of the radioactive antibody infusions. The average age was 69 years (range, 48-89 years), serum PSA was 55.9 ng/ml (range, 0-2,185 ng/ml), and serum PSMA was 0.32 (relative intensity levels range, 0.04-0.55). The initial therapies given were radical prostatectomy (55 scans), prostate radiation (74 scans), and/or hormonal therapy (77 scans). Twelve patients exhibited a negative scan. Local recurrence alone was identified in 58 scans (42.6%). Lymph node metastases were identified in 66 scans (48.5%). Of these, 21 had regional metastases alone, and 45 had distant lymph node metastases. Ten scans showed skip lymph node metastases without regional failure. PSA significantly correlated with negative, pelvic, and extrapelvic scan findings (P < or = 0.02). PSMA correlated best with pelvic recurrence and extrapelvic metastases in prostatectomized patients. Thirty-four patients had repeated scans for monitoring treatment response. Of these patients, 19 (56%) showed progression on the second scan, consistent with persistent increase in PSA and PSMA levels in all but 2 patients. Another 11 patients showed no change, and 4 patients showed partial remission, suggesting a response to the salvage treatment. All 20 positive prostate biopsies and 4 of the 7 positive lymph node biopsies correlated with ProstaScint findings, whereas 4 of the 6 patients with a negative biopsy had negative scans (i.e., 89% sensitivity and 67% specificity). Bone metastases were identified in 42 bone scans; 45% of these showed no lymph node metastasis on ProstaScint. In another 24 patients (57%), bone metastases were detected on ProstaScint examinations.

Aged↗
PubMed1998

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

BACKGROUND: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring. One such potential marker is prostate specific membrane antigen (PSMA). METHODS: A review was conducted to identify reports concerning evaluation of diagnostic applications of PSMA. RESULTS: PSMA is a membrane-bound glycoprotein that is highly restricted to the prostate. Immunohistochemical findings indicate that PSMA is a marker of epithelial cells of the prostate. This expression is increased in association with prostate carcinoma, particularly in hormone-refractory disease. Given its membrane-bound character, PSMA has been exploited as a marker for tumor detection by immunoscintiscanning with the 111In-labeled anti-PSMA monoclonal antibody 7E11.C5. Increased concentrations of 7E11.C5-reactive antigen are present in the serum of prostate carcinoma patients compared with healthy individuals; also, hematogenous circulating prostate carcinoma cells are detectable with reverse transcriptase-polymerase chain reaction analysis with primers specific for PSMA. New monoclonal antibodies specific for extracellular portions of the PSMA molecule currently are being utilized in applied studies. CONCLUSIONS: PSMA is a widely used marker for prostate epithelial cells. Its up-regulation in association with cancer, particularly in advanced cancer, is ideal for application as a prognostic marker. A variety of promising clinical applications utilizing PSMA have been or are being developed. In the future, these promise to have an important impact on cancer diagnosis and patient treatment.

Antigens, Surface↗
PubMed1998

The National Cancer Data Base report on prostate carcinoma after the peak in incidence rates in the U.S. The American College of Surgeons Commission on Cancer and the American Cancer Society.

BACKGROUND: Prostate carcinoma incidence has been declining since 1992 after a period of marked increase. Recent data from the National Cancer Data Base (NCDB) were examined to assess changes in prostate carcinoma patient characteristics and disease and treatment patterns coincidental to this decline. The NCDB is a program of the American College of Surgeons Commission on Cancer and the American Cancer Society that collects timely data from institutions representing every level of cancer care. METHODS: Data from 1114 hospitals regarding 103,979 patients diagnosed with prostate carcinoma in 1992 and from 1144 hospitals regarding 72,337 patients diagnosed in 1995 were studied. Patient and disease characteristics studied included age, race, American Joint Committee on Cancer stage, and tumor histologic grade. Trends in treatment and variations in treatment by region also were examined. RESULTS: The average age at diagnosis declined by 2 years over the period studied and the proportion of patients identified as African-American increased from 8.8% to 11.8%. The proportion of patients diagnosed with localized disease and the proportion of tumors of moderately differentiated histologic grade increased. The overall proportion of patients treated by radical prostatectomy increased and the use of external beam radiation treatment decreased. Substantial regional variation in treatment patterns was observed. The Pacific and Mountain state regions of the U. S. had the highest proportions of patients treated by radical prostatectomy although increases were occurring in other regions. Use of external beam radiation treatment was highest in the Northeast and Southeast states and was declining in the majority of regions. Use of brachytherapy radiation treatment by implantation of radioactive seeds was infrequent but increasing. CONCLUSIONS: Comparison of the basic characteristics of prostate carcinoma data from 1992 and 1995 shows that patients are being diagnosed at younger ages and earlier stages, the proportion of African-Americans has increased, and more patients are being treated for cure. Regional differences in patterns of care persist but may be moderating. The annual prostate carcinoma death rate in the U.S. has declined an average of 1% per year since 1990.

Age Factors↗
PubMed1998

Method for identifying prostate cells in semen using flow cytometry.

BACKGROUND: Prostate-specific antigen (PSA) cannot differentiate benign prostatic hyperplasia (BPH), from prostatitis, or prostate cancer in the range of 4.0-10 ng/ml. An accurate cytologic or histologic assessment is necessary to confirm the proper diagnosis. The nature of a biopsy tends to make it a selective test not frequently repeated. We are reporting a technique employing semen as a source for the differential diagnosis of prostate epithelial cells. METHODS: Eleven vasectomized and nonvasectomized prostate cancer patients provided semen samples (stage T1 to T2). Two patients provided repeat samples. In addition, 15 vasectomized or nonvasectomized individuals without evidence of disease provided semen samples. Three million cells fixed with 50% ethanol were stained by an antibody (7E11.C5) to prostate-specific membrane antigen (PSMA), Hybritech Antibody (399) to PSA, and cytokeratin 8 and 18. In addition to the antibodies described, a DNA stain To-Pro 3 was used to identify 2n-4n DNA containing cells. A dual laser, Becton Dickinson FACSCaliber cytometer, was used to analyze the samples. RESULTS: All semen specimens contained diploid, cytokeratin 18-positive epithelial cells regardless of disease status. A clear difference between prostate cancer and normal prostate cell samples was observed using staining with 7E11.C5. The ratio of prostatic cells in the total epithelial cell population (PSMA:cytokeratin ratios) was calculated for each specimen. A retrospective study of sixteen semen samples from 11 prostate cancer patients had a mean PSMA:cytokeratin ratio of 0.57, whereas the samples from 15 patients without evidence of cancer had a mean PSMA:cytokeratin ratio of 0.11. This difference was significant. PSA staining was variable and inconsistent. CONCLUSIONS: This report demonstrates that human semen contains prostate cells that can be characterized and used in the clinical diagnosis of prostate cancer.

Adult↗
PubMed1998

Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides.

BACKGROUND: A phase I trial involving patients with advanced prostate cancer was conducted to assess the safe administration of dendritic cells (DC) and HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 or -P2). Thirty-three of the phase I participants were subsequently enrolled in a phase II trial, which involved six infusions of DC pulsed with PSM-P1 and -P2 peptides. METHODS: Clinical monitoring was conducted up to 770 days from the start of the phase I study. Data collected included: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, and chest X-ray, as well as assays to monitor cellular immune responses. RESULTS: Nine partial responders were identified in the phase II study based on National Prostate Cancer Project (NPCP) criteria, plus 50% reduction of prostate-specific antigen. Four of the partial responders were also responders in the phase I study, with an average response duration of 225 days. Their combined average total response period was over 370 days. Five other responders were nonresponders in the phase I study. Their average partial response period was 196 days. CONCLUSIONS: The responses observed in the phase I and II clinical trials were significant and of long duration. The partial-responder group included patients who continued to respond from phase I, as well as those who started to respond during the phase II trial.

Alkaline Phosphatase↗