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W R Fair

Publications and source records attributed to W R Fair.

At least 91 records · Page 5Linked to original sources
PubMed1995

Sensitive detection of prostatic hematogenous tumor cell dissemination using prostate specific antigen and prostate specific membrane-derived primers in the polymerase chain reaction.

We developed a polymerase chain reaction based assay enabling sensitive detection of hematogenous tumor cell dissemination in patients with prostate cancer. We performed "nested polymerase chain reaction," amplifying messenger ribonucleic acid sequences unique to prostate specific antigen (PSA) and to the prostate specific membrane antigen, and compared the respective results. Prostatic tumor cells were detected in 2 of 30 patients (6.7%) by polymerase chain reaction with PSA derived primers, while prostate specific membrane primers detected tumor cells in 19 (63.3%). All 16 negative controls had negative PSA and prostate specific membrane polymerase chain reaction. Assays were repeated to confirm results, and polymerase chain reaction products were verified by deoxyribonucleic acid sequencing and Southern analysis. Patients harboring circulating prostatic tumor cells as detected by prostate specific membrane and not by PSA polymerase chain reaction included 7 of 13 previously treated by radical prostatectomy who had nonmeasurable serum PSA levels at the time of this assay. The significance of these findings with respect to future disease recurrence and progression will be investigated.

Base Sequence↗
PubMed1995

Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation.

OBJECTIVE: To define the role of salvage prostatectomy in patients who have locally recurrent prostate cancer following pelvic lymph node dissection and 125I implantation. PATIENTS AND METHODS: Over 1000 patients underwent 125I implantation for localized prostate cancer at the Memorial Sloan Kettering Cancer Center between 1970 and 1986. Salvage radical prostatectomy was performed in a highly selected group of 10 patients with locally recurrent disease. RESULTS: Three of the 10 patients had organ-confined residual prostate cancer following salvage radical prostatectomy. The remaining seven patients had extra-prostatic disease including four patients with positive surgical margins. Two patients with organ-confined disease and one with extracapsular tumour had no evidence of locally recurrent or metastatic disease and continue to have undetectable prostate-specific antigen (PSA) levels at 50, 44, and 31 months following salvage radical prostatectomy. After a mean follow-up of 30 months, the remaining seven patients had a rising PSA level consistent with locally persistent and/or metastatic disease (median 5 ng/mL; range 1.0-144). This PSA elevation occurred within 20 months of salvage radical prostatectomy (median 6 months). Two of these patients developed clinically evident bone metastases. CONCLUSION: Salvage radical prostatectomy, although technically feasible in highly selected patients, should not be widely advocated as an effective treatment option for patients with locally recurrent prostate cancer after 125I implantation.

Aged↗
PubMed1995

Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial.

PURPOSE: Superficial bladder tumors (stage Ta, T1, and Tis) may progress to invade the bladder muscle and cause death from metastatic cancer. Transurethral tumor resection (TURB) is the standard therapy for such tumors, but surgery alone may not prevent tumor progression. Intravesical therapy is widely used as an adjunct to TURB. Bacillus Calmette-Guérin (BCG) is the most active intravesical agent, but whether BCG prevents tumor progression and death from bladder cancer is unknown. PATIENTS AND METHODS: Between 1978 and 1981, 86 high-risk patients with superficial bladder cancer were randomly assigned to receive either TURB (n = 43) or TURB plus BCG (n = 43). Adverse tumor features for progression were equally distributed between the two groups. BCG was administered weekly for 6 weeks. Patients were evaluated every 3 to 6 months thereafter for progression to muscle invasion or metastasis. Control (TURB) patients with recurrent superficial tumors were eligible for crossover to the BCG arm. All patients have been monitored until event or for a minimum of 10 years (range, 10 to 14). RESULTS: The 10-year progression-free rate was 61.9% (95% confidence interval [CI], 47.2% to 76.7%) for patients treated with BCG and 37% (95% CI, 22.9% to 53.1%) for control patients. The median progression-free interval was not reached for the BCG group and was 46 months for the control group (P = .0063). Of 18 control patients crossed over to BCG (median, 29 months), 15 did not show tumor progression. TURB plus BCG resulted in a 10-year disease-specific survival rate of 75%, compared with 55% with TURB alone (P = .03). CONCLUSION: This study shows that intravesical therapy with BCG delays tumor progression and death from tumor in patients who present with superficial bladder cancer.

BCG Vaccine↗
PubMed1995

TAG-72 expression in primary, metastatic and hormonally treated prostate cancer as defined by monoclonal antibody CC49.

Monoclonal antibodies CC49 and B72.3, which recognize a tumor associated glycoprotein (TAG-72) related to sialyted Tn antigen, have been used in clinical trials for radionuclide imaging, and treatment of colon, breast and ovarian carcinoma. In addition, studies with CC49 in patients with metastatic hormone refractory prostate cancer have been initiated based on the observed expression of TAG-72 in primary prostate cancer. We examined whether TAG-72 expression is a common feature of primary, metastatic and hormonally treated prostatic carcinoma. Immunohistochemical analysis of 25 primary prostatic carcinomas confirmed previous data that 21 of 25 specimens (80%) were immunoreactive with CC49. CC49 staining was noted in all 6 well (Gleason score 2 to 4), 8 of 10 moderately (Gleason score 5 to 6) and 7 of 9 poorly (Gleason score 7 to 9) differentiated tumors. CC49 immunoreactivity was noted in 10 of 20 hormonally treated prostate cancers and in 21 of 25 tumors without hormonal therapy. Intense CC49 staining of prostatic intraepithelial neoplasia was present in all 5 specimens examined. In contrast to the primary lesion, many metastatic prostate cancers lacked detectable CC49 immunoreactivity. Of 24 pelvic lymph node metastases from different patients only 4 (17%) had significant CC49 staining and 5 others had rare CC49 positive cells. However, 6 of 12 bone metastases showed CC49 immune staining. One specimen from an anaplastic locally recurrent tumor showed no reactivity. To our knowledge we present the first analysis of TAG-72 expression in a large series of patients with hormonally treated and metastatic prostate cancer, the most likely candidates for CC49 immunotherapy. Our findings that lymph node and bone metastases from prostate cancer are less likely to express significant amounts of TAG-72 than primary prostate cancer suggest that pretreatment biopsy typing for TAG-72 may be necessary to optimize the results of ongoing CC49 imaging and therapy studies.

Adenocarcinoma↗
PubMed1994

Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays.

A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.

Antigens, Neoplasm↗
PubMed1994

Prostate adenocarcinoma in men younger than 50 years. A retrospective review of 151 patients.

BACKGROUND: Prostate adenocarcinoma is predominantly a disease of older men. Males younger than 50 years account for 1% of all patients with prostate cancer. The authors retrospectively examined cases of prostate adenocarcinoma in patients younger than 50 years of age to determine the natural history and prognosis of this malignancy in the younger population. METHODS: The medical records of 151 patients were reviewed, with particular attention to age and year at diagnosis, race, symptoms at presentation, family history of prostate cancer, histologic grade, clinical and pathologic stage, treatment modality, and clinical outcome. RESULTS: Univariate analyses demonstrated a significant correlation between higher disease stage (P = 0.0001), higher tumor grade (P = 0.0001), earlier year of diagnosis (P = 0.01), symptoms at presentation (P = 0.0001), and race (P = 0.01) with shorter disease-specific survival. However, multivariate analysis revealed that only stage and grade were statistically significant predictors for poor prognosis after controlling for other variables. With a one-unit increase of stage or grade, the risk of death from disease increases 2.2 or 1.9 times, respectively. CONCLUSION: These data suggest that patients younger than 50 years with prostate cancer present with similar symptomatology, histologic grade, and disease stage as the older population. Patients with disease confined to the prostate have a relatively good disease-specific survival but remain at risk for death even 15 years after diagnosis. When carcinoma escapes the confines of the prostate, the prognosis is uniformly poor.

Adult↗
PubMed1994

Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines.

This study explored the use of cytokine gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology and responds to treatment in a manner similar to that of its human counterpart. In a previous study we have shown that interleukin 2 (IL-2)-secreting, irradiated, MBT-2 cell preparations were capable of curing animals from orthotopically established tumors and engendered protective immunological memory in the cured animals. In this study we have compared the effectiveness of several cytokines and found that while IL-1 alpha, IL-1 beta, and gamma-interferon were only weakly effective in the therapeutic vaccination protocol, granulocyte-macrophage colony-stimulating factor was almost as effective as but not superior to IL-2, as reported previously for another tumor model system. Induction of cytotoxic T-lymphocyte correlated only poorly with the therapeutic benefit of the cytokine gene-modified tumor cell preparations, questioning its prognostic value for the development of improved genetically modified tumor vaccines.

Animals↗
PubMed1994

The role of pelvic lymphadenectomy and radical cystectomy for lymph node positive bladder cancer. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: The impact of pelvic lymph node dissection (PLND) on the survival of patients with lymph node positive bladder cancer is controversial. METHODS: The authors retrospectively analyzed the long term and disease free survival among 140 patients with lymph node positive disease having radical cystectomy and bilateral PLND at the Memorial Sloan-Kettering Cancer Center between 1980 and 1988. They also sought to identify prognostic variables for recurrence and survival. RESULTS: Of the 140 patients, 36 (25.7%) were found to be tumor free, with 22 (15.7%) followed longer than 5 years. Regression analysis identified P-category as the only prognostic parameter influencing survival. Patients with tumors confined to the bladder (< or = P3a) had a 52.6% 5-year survival rate compared with 23.4% among those with extravesical (> or = P3b) tumors. N-category was a significant predictor for recurrence but not survival. CONCLUSIONS: As judged from this analysis, radical cystectomy and a systematic PLND alone can provide favorable outcome in some patients with regional nodal metastases from bladder cancer. The survival advantage is most pronounced in patients with low stage primary tumors. Stage migration and patient selection may have biased these findings.

Combined Modality Therapy↗
PubMed1994

Expression of the prostate-specific membrane antigen.

We have recently cloned a 2.65-kilobase complementary DNA (cDNA) encoding the prostate-specific membrane antigen (PSM) recognized by the 7E11-C5.3 anti-prostate monoclonal antibody. Immunohistochemical analysis of the LNCaP, DU-145, and PC-3 prostate cancer cell lines for PSM expression using the 7E11-C5.3 antibody reveals intense staining in the LNCaP cells with no detectable expression in both the DU-145 and PC-3 cells. Coupled in vitro transcription/translation of the 2.65-kilobase full-length PSM cDNA yields an M(r) 84,000 protein corresponding to the predicted polypeptide molecular weight of PSM. Posttranslational modification of this protein with pancreatic canine microsomes yields the expected M(r) 100,000 PSM antigen. Following transfection of PC-3 cells with the full-length PSM cDNA in a eukaryotic expression vector, we detect expression of the PSM glycoprotein by Western analysis using the 7E11-C5.3 monoclonal antibody. Ribonuclease protection analysis demonstrates that the expression of PSM mRNA is almost entirely prostate specific in human tissues. PSM expression appears to be highest in hormone-deprived states and is hormonally modulated by steroids, with 5-alpha-dihydrotestosterone down-regulating PSM expression in the human prostate cancer cell line LNCaP by 8-10-fold, testosterone down-regulating PSM by 3-4-fold, and corticosteroids showing no significant effect. Normal and malignant prostatic tissues consistently show high PSM expression, whereas we have noted heterogeneous, and at times absent, expression of PSM in benign prostatic hyperplasia. LNCaP tumors implanted and grown both orthotopically and s.c. in nude mice abundantly express PSM, providing an excellent in vivo model system to study the regulation and modulation of PSM expression.

Adrenal Cortex Hormones↗
PubMed1994

Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines.

Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that active immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer.

Adenocarcinoma↗
PubMed1994

An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer.

In order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327-MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene-modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327-MatLyLu tumors.

Animals↗
PubMed1994

Detection of occult micrometastases in the bone marrow of patients with prostate carcinoma.

A panel of three monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (T16, C26, and AE-1) was used in a sensitive immunohistochemical assay to detect tumor cells in bone marrow aspirates from 20 patients with prostate cancer. Bone marrow aspirates from 2/9 (22%) patients with localized prostate cancer (stage B, 0/5; Stage C, 2/4), and 4/11 (36%) patients with metastatic prostate cancer (Stage D1, 0/7 patients; Stage D2, 4/4 patients) had antigen-positive cells in their bone marrow. The patients with localized disease had conventional examinations for metastases, including radioisotope bone scans and examination of bone marrow cytology, which were negative. The serum prostatic specific antigen (PSA) level appeared to correlate with the presence of micrometastases. Those patients with localized disease and antigen-positive cells in the bone marrow had an average serum PSA level of 26.6 ng/ml, while the average serum PSA level in patients without antigen-positive cells was 12.3 ng/ml. In addition, the number of antigen-positive cells detected appeared to correlate with the stage of disease; patients with Stage C prostate cancer had an average of 10 antigen-positive cells per one million bone marrow elements, while patients with Stage D2 disease had an average of 25 antigen-positive cells per one million bone marrow elements. We have demonstrated that immunohistochemical staining of bone marrow aspirates can detect occult bone marrow metastases in patients with apparently localized prostate cancer. Further follow-up of these and a larger number of patients will be require to determine the potential clinical significance of this finding.

Acid Phosphatase↗
PubMed1994

Bladder cancer: advances in biology and treatment.

Integrating systemic chemotherapy in the treatment of patients with invasive bladder cancer is essential to improve survival because the majority of deaths are from systemic relapse. However, as experience with invasive tumors evolves, it is clear that treatment recommendations need to be tailored to an individual patient based on metastatic risk and, ideally, sensitivity to treatment. For those with tumors that do not extend through the bladder wall, standard therapy remains radical surgery. Nevertheless, encouraging results are being reported with increasing frequency using strategies designed to preserve bladder function through a variety of means. Crucial to the recommendation of a specific approach for an individual is improving our ability to define prognosis prior to initiating treatment. Patients with a high risk of systemic recurrence generally require chemotherapy, although the optimal route of integration, pre vs. post-operatively, remains controversial. In those patients who require it, chemotherapy can be administered more safely with the concomitant administration of hematopoietic growth factors. These factors alone, however, are unlikely to improve overall survival. Crucial to the latter effort will be the identification of more active agents, improving our understanding of intrinsic and acquired resistance to chemotherapy, and better delivery of the chemotherapeutic agents currently available. Of equal importance, is the enrollment of patients in clinical trials. These can include large scale randomized comparisons with using a survival end-point, as well as new therapies in high risk populations. The latter would include patients with advanced T3b, T4 and N+ disease, with a high risk of metastatic failure, and low complete response proportions to presently available regimens.

Antineoplastic Agents↗
PubMed1994

Expression of transforming growth factor-alpha and the epidermal growth factor receptor in human prostate tissues.

Cells respond to certain soluble factors that bind to cell surface receptors possessing intrinsic tyrosine kinase activity. Overexpression of these molecules has been associated with tumor progression. Enhanced prostatic cancer cell growth in vitro has been reported in the presence of certain growth factors. To characterize the patterns of expression of the epidermal growth factor receptor (EGFr) and transforming growth factor-alpha (TGF alpha), we studied tissue from 107 prostate specimens using immunohistochemistry. We observed that epithelial cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but were unreactive for TGF alpha, while stroma cells in these tissues express TGF alpha but not EGFr. However, coexpression of EGFr and TGF alpha was identified in 22 of 46 prostatic adenocarcinomas studied. These results suggest that the major mode of action of EGFr/TGF alpha in normal and benign prostate is that of a paracrine or juxtacrine loop, the ligand being expressed in the stroma cells and the receptor in the epithelial cells. Since a subset of prostatic carcinomas coexpressed the ligand and the receptor in their tumor cells, it is suggested that an independent autocrine signaling mechanism may occur and grant a selective advantage for the growth of prostate cancers.

Adenocarcinoma↗
PubMed1994

Positive urinary cytology following a complete response to intravesical bacillus Calmette-Guerin therapy: pattern of recurrence.

The pattern of disease recurrence was examined in 75 patients with clinically undetectable positive urinary cytology results following a complete response to intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. A complete response was defined as negative cystoscopy and biopsy findings, urine cytology and flow cytometry (when available) for at least 1 year following therapy. Urinary cytology was positive in the absence of clinical disease at a median of 25 months (range 12 to 96) after BCG administration. Clinically recognizable disease (defined by a positive biopsy or visible papillary tumor) developed at a median of 6 months (range 2 to 60) after positive cytology was detected in 62 patients (83%), while 13 (17%) had persistently positive cytology results without an obvious source at a median of 6 months (range 2 to 29). The bladder was the single most common site of recurrence, with 39 recurrences developing in 36 patients (58%, 3 of whom had recurrent cancer after a complete response to each of 2 separate courses of BCG): 30 (77%) were superficial (stages Ta in 2, Tis in 25, Tis/T1 in 2 and T1 in 1) and 9 (23%) were invasive (stage T2+). Median interval to the detection of bladder recurrence following a positive cytology result was 6 months (range 2 to 50). Upper urinary tract disease developed at a median of 7 months (range 2 to 41) in 11 patients (18%), while 7 (11%) had a prostatic recurrence at a median of 5 months (range 2 to 60). There were 9 synchronous bladder and prostate (5) or upper tract (4) recurrences in 8 patients (13%) at a median of 22 months (range 2 to 40) in the former group and 15.5 months (range 3 to 20) in the latter group. Overall, of 75 sites of recurrence in 62 patients 48 (64%) were in the bladder, 15 (20%) in the upper urinary tract and 12 (16%) in the prostate. High risk patients with superficial bladder cancer who have clinically unconfirmed positive urinary cytology results following a complete response to intravesical BCG therapy require aggressive evaluation of intravesical and extravesical sites to detect the presence of persistent or progressive in situ or invasive disease.

BCG Vaccine↗