RESUMEN
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.
Asunto(s)
Antígenos de Superficie , Vacunas contra el Cáncer/uso terapéutico , Carboxipeptidasas/uso terapéutico , Antígeno HLA-A2/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Vacunas Sintéticas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/administración & dosificación , Antígenos de Neoplasias/uso terapéutico , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Vacunas contra el Cáncer/administración & dosificación , Carboxipeptidasas/administración & dosificación , Células Dendríticas , Glutamato Carboxipeptidasa II , Antígeno HLA-A2/administración & dosificación , Hormonas/uso terapéutico , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Cintigrafía , Resultado del Tratamiento , Vacunas Sintéticas/administración & dosificaciónRESUMEN
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.
Asunto(s)
Antígenos de Superficie , Citometría de Flujo/métodos , Próstata/citología , Enfermedades de la Próstata/diagnóstico , Semen/citología , Adulto , Biomarcadores de Tumor/análisis , Carboxipeptidasas/análisis , Diagnóstico Diferencial , Glutamato Carboxipeptidasa II , Humanos , Queratinas/análisis , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Antígenos de Neoplasias/uso terapéutico , Antígenos de Superficie , Carboxipeptidasas/uso terapéutico , Células Dendríticas/trasplante , Neoplasias de la Próstata/terapia , Fosfatasa Alcalina/metabolismo , Biomarcadores de Tumor , Células Cultivadas , Estudios de Evaluación como Asunto , Glutamato Carboxipeptidasa II , Humanos , Masculino , Monitoreo Fisiológico , Resultado del TratamientoRESUMEN
BACKGROUND: Metastatic prostate cancer clinical evaluation is difficult. A revaluation of new prostate markers with regard to bone scans was performed. METHODS: Serial markers, including bone alkaline phosphatase (BAP), total alkaline phosphatase (TAP), prostate-specific antigen, total (PSA) and free (fPSA), and prostate-specific membrane antigen (PSMA), were obtained in patients under evaluation and treatment for possible or known metastatic prostate cancer. These were correlated with bone scan results (BSR). RESULTS: Seventy patients were observed from mid-October 1996-January 1997, during which time 171 serum samples were obtained and correlated with semiquantitative bone scan status. PSA and fPSA provided some correlation with BAP and BSR, but only at high levels (> 16-50 ng/ml). Receiver-operating curve (ROC) analysis demonstrated that BAP and TAP had a significant discriminating ability for positive and negative bone scans (> .78), compared to PSMA, PSA, and fPSA. However, percent BAP and TAP only correlated with BSR at a level above six lesions. As the lesions detected by BSR increased, the correlation increased. CONCLUSIONS: BAP is a valuable marker for clinical response evaluations to use in the serial follow-up of patients with metastatic prostate cancer, and correlates well with the bone scan as the number of lesions increase to > 6. PSA or fPSA show comparable results, but only at high levels (> 16-50 ng/ml).
Asunto(s)
Fosfatasa Alcalina/análisis , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Neoplasias Óseas/secundario , Huesos/química , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/química , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Antígenos de Neoplasias/sangre , Antígenos de Superficie/sangre , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Neoplasias Óseas/diagnóstico por imagen , Huesos/diagnóstico por imagen , Huesos/enzimología , Estudios de Seguimiento , Glutamato Carboxipeptidasa II , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Curva ROC , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: We recently conducted a phase I clinical trial administering autologous dendritic cells pulsed with prostate-specific membrane antigen (PSMA) peptides to advanced prostate cancer patients. Participants were divided into 5 groups receiving 4 or 5 infusions of peptides alone (PSM-P1 or -P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or -P2 (groups 4 and 5, respectively). Seven partial responders were observed. Follow-up evaluation of these responders is presented in this report. METHODS: Clinical monitoring for hematological studies and prostate markers was conducted up to 370 days from the start of the phase I study. Data collected include: lymphocyte, hematocrit, alkaline phosphatase, prostate-specific antigen (PSA), free PSA, and PSMA levels. RESULTS: Groups 4 and 5 (patients infused with DC pulsed with PSM-P1 or -P2) represented 5/7 responders. The length of response was between 100 days (1 patient) to 200 days or above (6 patients). Four patients still remained responsive at the end of the period of observation. CONCLUSIONS: The responses observed in this phase I clinical trial are significant and of long duration. Most of the responders were in treatment groups infused with DC pulsed with PSM-P1 or -P2, suggesting the requirement of both components for effective immunotherapy.
Asunto(s)
Células Dendríticas/trasplante , Fragmentos de Péptidos/uso terapéutico , Antígeno Prostático Específico/uso terapéutico , Neoplasias de la Próstata/terapia , Fosfatasa Alcalina/sangre , Secuencia de Aminoácidos , Biomarcadores/sangre , Células Cultivadas , Estudios de Seguimiento , Hematócrito , Humanos , Inmunoterapia/efectos adversos , Infusiones Intravenosas , Recuento de Linfocitos , Masculino , Fragmentos de Péptidos/administración & dosificación , Antígeno Prostático Específico/administración & dosificación , Factores de Tiempo , Trasplante AutólogoRESUMEN
A prostate cancer screening study of 315 asymptomatic men comparing digital rectal examination and transrectal ultrasound identified 23 cancers, for a detection rate of 7.3%. Of the cancers 17 (5.4%) were diagnosed by digital rectal examination. Contrary to the experience of others, this was a higher rate than achieved by transrectal ultrasound (14 cases or 4.4%). Systematic multiple needle biopsies of both lobes with ultrasound guidance were routinely performed. As a result of this technique 7 of 23 cancers (30%) were fortuitously diagnosed. In addition, only unilateral disease was suspected in 4 of 7 patients with bilateral disease on biopsy. Digital rectal examination and transrectal ultrasound identified the same number of patients with small (less than 1.5 cm.) cancers, contrary to other reports that found transrectal ultrasound to be superior. Digital rectal examination is considered an effective screening examination, equivalent to transrectal ultrasound and preferable because of lower cost. An algorithm for screening is outlined with digital rectal examination and prostate specific antigen determinations.
Asunto(s)
Palpación , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Algoritmos , Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Biopsia con Aguja , Estudios de Evaluación como Asunto , Humanos , Masculino , Persona de Mediana Edad , Próstata/inmunología , Próstata/patología , Antígeno Prostático Específico , Recto , UltrasonografíaRESUMEN
Volume and distribution of prostatic carcinoma were measured in 30 radical prostatectomy specimens. Obtaining these data was facilitated by the use of whole tissue mounts. Similar measurements were obtained from preoperative transrectal ultrasound studies. With this information the ability of digital rectal examination and transrectal ultrasound to predict tumor burden was analyzed. It was concluded that both of these examinations are poor predictors of tumor volume, distribution and pathological stage. Preoperative prostate specific antigen levels were correlated with the pathological data. It appeared that prostate specific antigen levels of greater than 10 presage [corrected] tumor volumes of greater than 3 cc, and that levels of more than 50 are suggestive of stages C and D disease.
Asunto(s)
Antígenos de Neoplasias/análisis , Carcinoma/diagnóstico , Examen Físico , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Ultrasonografía , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patologíaRESUMEN
A simplified operation for female stress incontinence, using a pair of double-prong needles, is described. A 90.4 per cent cure was achieved in 62 patients followed for a mean of 11.2 months. Merits of this procedure include operative simplicity and brevity, short hospitalization and a high rate of cure.