Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of prostate cancer in the UK is increasing, and the disease is being detected more often in younger patients (e.g. from routine PSA measurement during health-care screening). Left untreated, a significant proportion of patients will undergo progression of their disease locally and/or develop metastases. Modern imaging techniques have greatly aided the assessment of early prostatic cancer, enabling both accurate assessment of the primary tumour and giving valuable information regarding lymph node metastases. PSA measurements are also extremely helpful, and this has replaced acid phosphatase as a marker for prostatic malignancy. Controversy still remains, however, over the best form of management. Radical prostatectomy undoubtedly produces the best results in the literature, but the patients are highly selected (e.g. those with nodal metastases are excluded) and some patients with well differentiated tumours may have been over-treated, as they may have been expected to do well with surveillance alone. Full clinical trials are required in identically staged patients to assess the relative merits of surveillance, radiotherapy and surgery, and this should now be possible with recent advances in imaging techniques.
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PMID:Current trends in the management of localised prostate cancer. 130 88

The prevalence of neural elements in prostatic carcinoma and their effects on the behavior of the lesion have recently been recognized. Recent reports suggest that chromogranin-A- and neuron-specific enolase-expressing tumors have an earlier progression and a lower response rate to hormonal therapy. The extreme presentation of this tumor is presumed to be small cell carcinoma of the prostate. This bombesin-secreting tumor, which has a characteristic clinical picture of early visceral involvement, wide-ranging metastases, and a relatively low rate of expression of PSA and PAP, is highly responsive to chemotherapy. The relatively high rate of expression of neural elements in primary prostatic carcinoma is discordant with the low frequency of clinical small cell carcinoma of the prostate. In order to account for these differences, one can assume that neural elements may play a role in the progression of this disease by either developing their own neoplastic process (small cell carcinoma of the prostate) or, in the majority of cases, causing paracrine progression of the tumor. Bombesin is typically secreted by small cell carcinoma of the lung and possibly by the prostate. It has been shown to be a growth factor mediating the progression of this disease in a number of experiments. Preclinical data demonstrate increased invasiveness and increased proliferation associated with bombesin in the treatment of prostatic carcinoma. Based on the hypothesis that neural peptides may be important mediators of androgen-independent growth of prostatic carcinoma as well as predicting poor prognosis, inhibition of these factors may represent a therapeutic strategy of relevance for the treatment of patients with prostatic carcinoma.
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PMID:The inhibition of the paracrine progression of prostate cancer as an approach to early therapy of prostatic carcinoma. 133 63

Activity and side-effects of clodronate (Ostac), an inhibitor of osteoclastic bone resorption, were recorded in an open prospective uncontrolled study on 35 patients with metastatic prostatic cancer. All patients had progressive symptomatic bone metastases despite prior hormone therapy. Clodronate was initially administered i.v. for 8 days with 300 mg/day. This was followed by a daily oral administration of 1600 mg. The analgesic effect was evaluated by using a visual analogue scale and by recording the daily consumption of analgesic drugs. Karnofsky index and routine blood examinations, including PSA, were assessed. Repeated bone scans and radiological evaluations were performed. An improvement in pain was observed in 71% of the patients. The mean duration of improvement was 4 weeks. Average survival time was 12 weeks. There were no side-effects after i.v. administration. Slight gastrointestinal discomfort was observed in 3 patients after oral administration. No effect was observed on the extent or biology of the metastases. Clodronate is an effective drug for palliative treatment of symptomatic bone metastases of prostatic carcinoma. It causes fewer and less pronounced side effects than other palliative drug therapies.
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PMID:[Clodronate in the palliative therapy of bone-metastasized prostatic carcinoma]. 137 55

The currently available prognostic factors allow the identification of patients who are destined to do poorly with primary hormone therapy. Standardization of these factors is required so that they become incorporated into routine practice. For patients who relapse in osseous sites radiolabeled diphosphonates are one therapeutic alternative that can provide palliation. Future use will be directed to optimize treatment schedules, and use earlier in the course of the disease so that more durable palliation of bony metastases can be achieved. Evolving data on the use of PSA show that elevations antedate clinical relapse for most patients. In these cases, sequential changes can be used to assess therapeutic effects, which in turn can allow novel therapies to be screened more rapidly in the clinic. Criteria for the degree of change that is indicative of response must be standardized. Preliminary data suggest a 50% decline be the minimum that is used. The results with agents such as suramin, which interrupts autocrine and paracrine growth factor loops, are a therapeutic strategy that need further study. Future efforts will focus on defining which patients are best suited for specific therapeutic approaches.
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PMID:Therapeutic alternatives for hormone-refractory prostatic cancer. 137 15

Pre-operative serum prostate specific antigen (Tandem-R assay), T category, Gleason score and the metastatic (M1) status of a consecutive series of 60 patients with newly diagnosed carcinoma of the prostate were studied prospectively. The results revealed that, of these variables, pre-operative serum PSA (greater than 100 ng/ml) was the single most important indicator of metastatic disease, with 100% predictive value. With this alone, 83.3% of M1 disease could be correctly identified. For the remaining 17%, however, we advocate a high index of suspicion if the tumour is T3-T4 category on digital rectal examination (predictive value = 71.4%) and has a high grade with a Gleason score 8-10 (predictive value = 81%).
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PMID:Identification of metastatic disease by T category, gleason score and serum PSA level in patients with carcinoma of the prostate. 137 66

We retrospectively evaluated 51 prostate cancer patients found to have pelvic lymph node metastases at the time of pelvic lymphadenectomy and 125I implantation. All of them were followed until death or for a minimum of 70 months. Rabbit polyclonal anti-PSA, anti-PAP, anti-PSP-94, and mouse TURP-27 monoclonal antibodies were used in immunohistochemical evaluation of the metastatic lesions. In addition, Gleason grade and ploidy were assessed and correlated. No tumor with a Gleason grade of less than 7 could be found in the metastatic lymph nodes. Time to progression (P = .003), disease-specific survival (P = .009), and overall survival (P = .003) were significantly shorter in patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10). In the PSA study, patients whose tumors were reactive in more than 75% of cancer cells experienced significantly longer survival than those with less than 75% of cancer cells expressing PSA (P = .0006 log rank test). The means of overall survival +/- SEM were 71.5 +/- 5.0 and 34.9 +/- 5.4 months, respectively. Similar correlations were found with disease-specific survival and time to progression. Patterns of PAP expression and TURP-27 reactivity were not prognostically useful, whereas PSP-94 expression may add some additional information. These data suggest that evaluation of tissue PSA heterogeneity in lymph node metastases may offer additional prognostic information on prostate cancer patients. Better prediction of individual prognosis may be possible with the combined use of Gleason grade, flow cytometry, and PSA expression.
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PMID:Prognostic significance of antigenic heterogeneity, Gleason grade, and ploidy of lymph node metastases in patients with prostate cancer. 137 12

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells.
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PMID:The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer. 137 59

Natural killer (NK) cell activity was studied together with tumor marker serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin concentrations in treated prostate cancer patients. NK cell activity data were correlated with tumor stage (stage D0 + D1 versus stage D2) and showed statistically insignificant differences. Both tumor progression and stabilization of metastatic disease, triggered by the application of more appropriate therapy in progressive subjects, yielded low NK activity data. By contrast, normal NK activity was found during both partial remission of stage D2 tumor and stabilization of the same disease, after an initial period of tumor remission. Differences between NK activity data from the aforementioned two groups are statistically significant (P less than 0.01). In subjects examined, the application of NK activity assay to those with advanced disease reflected changes in the outcome of the treatment more closely than it did routine tumor marker assessment. The activity of NK cells seems unaffected by changes in basal blood estradiol, cortisol, testosterone, and prolactin concentrations that occur during therapy with pharmacological agents (estradiol, cyproterone acetate, diethylstilbestrol, and flutamide) and during surgical castration. The reported NK activity recordings in treated prostate cancer patients might be indicative of the presence of tumor cells in the circulation. If this holds true, the measurement of NK activity would appear to furnish urological oncology with a new tool for early, rapid recognition of progressive metastatic tumors.
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PMID:NK cell activity in treated prostate cancer patients as a probe for circulating tumor cells: hormone regulatory effects in vivo. 138 13

Correlation between findings on bone gammagraphy and PSA levels in 144 patients with untreated prostate cancer are analyzed. With prevalence of metastatic disease in 57.6% cases and considering the predictive cut value of metastasis to be 20 ng/ml, there were positive and negative predictive values of 64.9% and 73.9%, with a diagnostic confidence of 66.6%. We conclude that bone gammagraphy is essential for staging prostate cancer even in patients with PSA below 20 ng/ml.
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PMID:[Can we do without bone gammagraphy in the staging of prostatic cancer?]. 150 19

Between 1977 and 1991, 20 patients with radical prostatectomy for adenocarcinoma of the prostate and palpable, biopsy-proven local recurrence without evidence of metastases underwent radiotherapy. Of these patients 16 were treated with orchiectomy combined with irradiation and four patients underwent irradiation alone. Local control, as determined by rectal palpation was achieved in 19/20 patients. Eleven patients are still alive without disease. Disease-free survival (determined since 1987 including PSA) was 68% for five years and 41% for ten years. 6/9 patients have died with cancer, three patients died intercurrent free of disease. Overall survival remained 51% for five years and 31% for ten years. Prevention of local recurrence is of great importance and these data support the adjuvant post-operative irradiation in defined patients at risk.
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PMID:Radiotherapy of local recurrence following radical prostatectomy. 162 Dec 11


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