Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anatomical radical retropubic prostatectomy currently may be performed with low morbidity and mortality. The nerve-sparing aspect of the anatomical radical retropubic prostatectomy has allowed preservation of potency in the majority of men with localized prostate cancer. Overall potency rates of up to 71% may be achieved without compromising the complete eradication of cancer. Prostate cancer control with nerve-sparing surgery is similar to that reported for the standard radical retropubic prostatectomy. Inaccurate clinical staging of prostate cancer and the inability to determine tumor involvement of the neurovascular bundle have made it difficult to decide with certainty preoperatively which patients should undergo preservation versus wide excision of the neurovascular bundle. Some of the controversies that may determine utility of nerve-sparing radical prostatectomy include the impact of prostate cancer capsular penetration and positive surgical margins on tumor progression and patient survival. The selection of the ideal patient who has clinically localized prostate cancer for nerve-sparing radical prostatectomy has been improved by using as guidelines such preoperative factors as serum prostate-specific antigen tumor grade and the presence of perineural invasion on biopsy, and by using tumor location and volume to help predict true pathological stage. Other preoperative studies including transrectal ultrasound, computed tomography, and magnetic resonance imaging are generally not helpful.
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PMID:Current results and patient selection for nerve-sparing radical retropubic prostatectomy. 852 Nov 34

To date androgen receptor (AR) expression and structure in human prostatic cancer have been studied in primary tumor specimens and in cell lines. Investigation of alterations in the androgen-signalling transduction cascade in prostatic carcinoma metastases is important to improve our understanding of tumor progression towards androgen insensitivity. In the present study we have collected data comparing AR expression in both the primary tumors and the respective pelvic lymph node metastases. Formalin-fixed and paraffin-embedded tissues derived from the primary tumors and positive lymph nodes of 12 patients undergoing radical prostatectomy were immunostained for the AR and prostate-specific antigen (PSA). AR expression was evaluated with the polyclonal antibody PG-21, which is directed against amino acid 1-21 in the N-terminal region of the AR. All primary tumors stained for the AR. In 8 of the 12 lymph nodes examined more than 50% of the tumor cells were AR positive and displayed a uniform staining pattern; in one lymph node metastasis remarkable heterogeneity in AR expression was observed. In two cases less than 10% of the tumor cells stained for the AR. In one case the lymph node metastasis was immunohistochemically negative for the AR, whereas the primary tumor obtained from the same patient displayed intense staining for the AR. PSA was expressed in all metastases and primary tumors. Our data demonstrate that loss of the AR in lymph node metastases from prostatic carcinoma is a rare event.
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PMID:Androgen receptor status of lymph node metastases from prostate cancer. 860 94

So far, no curative treatment is available for hormone-refractory prostate carcinoma. Therapy is thus focused on alleviating symptomatic tumor progression with the aim of improving quality of life. Therefore, anthracyclin-derived mitoxantrone was administered to 25 patients with hormone-refractory prostate carcinoma and symptomatic progressive disease. After a median treatment of 13 weeks, a median of 4 cycles and a follow-up of 14 months, 48% of the patients (12/25) reported improvement in tumor-related pain; in 60% (15/25) there was improvement of the self-assessment symptom score and 32% of the patients (8/25) gained weight. Additionally, partial tumor response with regression of lymph-node metastases occurred in 3/25 patients (12%). In 10/25 patients the serum level of prostate-specific antigen (PSA) decreased as well as the alkaline phosphatase (AP) in 7/25 patients. Side effects subsequent to chemotherapy were leucopenia WHO grade III in 25% of the patients and thrombocytopenia WHO grade III in 3/25 and grade V (treatment-related death) in 1/25 patients. Non-hematological toxicity occurred in 2 patients (cardiotoxicity n = 1, nephrotoxicity n = 1, WHO grade II each).
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PMID:[Therapy of hormone refractory prostate carcinoma with mitoxantrone. A clinical phase II study]. 865 Aug 48

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.
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PMID:Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases. 895 15

This is Part 2 of a three-part review and deals with tumorigenic cell lines. Several immortalized and malignant adult human prostatic epithelial cell lines have been recently developed. The three most widely used carcinoma cell lines-DU-145, PC-3, and LNCaP-developed between 1977 and 1980, have greatly contributed to our current understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with Simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in the initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. The nontumorigenic cell lines were discussed in Part 1 [1]. This review summarizes the characteristics of several currently available tumorigenic, adult human prostatic epithelial cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications Part 2. Tumorigenic cell lines. 901 37

This is Part 3 of a three-part review. It deals with the possible role of oncogenes and suppressor genes in human prostate carcinoma as well applications of nontumorigenic and tumorigenic human prostate cell lines described in Parts 1 and 2 [1,2]. Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance and its reversal and chemoprevention. This review summarizes some applications of the currently available immortalized, non-tumorigenic as well as the tumorigenic adult human prostatic epithelial cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part 3. Oncogenes, suppressor genes, and applications. 905 Nov 52

Understaging is commonly associated with therapeutic failure of surgical intervention in apparently localized prostate cancers. Methods that specifically detect prostate cancer cells in the circulation may be able to identify metastatic cancers and thus aid in the selection of the most adequate therapy. The high sensitivity and specificity of the reverse transcriptase-polymerase chain reaction (RT-PCR) encouraged various groups to investigate the mRNA expression of prostate-specific markers in the peripheral blood of patients with prostate cancer. However, probably due to methodological differences, many contradictory results have been obtained with the markers studied so far: prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM). For this reason, clinical decisions should not be based yet on RT-PCR results. Future research and long-term follow-up on the patients may point out whether RT-PCR assays, following appropriate standardization, will have an additive value in prostate cancer staging and in prediction of tumor progression.
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PMID:Clinical usefulness of RT-PCR detection of hematogenous prostate cancer spread. 944 45

The detection of micrometastasis of prostate cancer could help to decide more appropriate therapeutic strategies in an individual patient. We have developed a flow cytometric method for detecting cytokeratin-positive cells in the peripheral blood before, during and after radical prostatectomy in patients with prostatic carcinoma. By means of this technique we were able to detect a higher number of cytokeratin-positive cells in the intraoperative blood sample than in the pre- and postoperative blood sample in 15 patients with prostate cancer (P < 0.05). Our results show an increase in the number of cytokeratin-positive cells with increasing tumor stage and grade, as well a good correlation of prostate-specific antigen (PSA) value with the number of cytokeratin-positive cells (r > 0.6). Our results underline the importance of no-touch techniques at prostatectomy to minimize release of tumor cells into the circulation during surgery. In the light of our results we consider that the indication for cell savers during radical prostatectomy should be reevaluated. The possibility of detecting single metastatic cells in peripheral blood will enable better individual patient management, and open up new modalities for diagnosing early prostate cancer and enhancing patient monitoring in relapse and tumor progression.
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PMID:Detection of circulating prostatic cells during radical prostatectomy. 944 46

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.
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PMID:Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. 960 66

Cribriform neoplasia of the prostate can be recognized easily. However, controversy persists regarding terminology, particularly with the intraductal spread of cribriform neoplasia; some consider this "intraductal carcinoma," whereas consensus meetings defined these lesions as high-grade cribriform prostatic intraepithelial neoplasia (HGCP). This study attempts to identify the incidence and clinical significance of HGCP and cribriform carcinoma (CC) by evaluating 114 radical prostatectomy specimens. Cases were divided into three histologic groups for statistical analysis: (1) pure acinar carcinoma: infiltrating acinar carcinoma without evidence of cribriform neoplasia; (2) CC: acinar carcinoma with CC; and (3) HGCP: acinar carcinoma with HGCP. High-grade cribriform prostatic intraepithelial neoplasia was defined as the presence of neoplastic cells spanning the entire lumen in a cribriform configuration in which a basal cell layer could be shown by immunohistochemistry. Similar areas in which no basal cell layer could be seen were diagnosed as CC. The incidence of cribriform neoplasia was 38% (43 of 114). The incidences of HGCP and CC were 13% (15 of 114) and 25% (28 of 114), respectively. Univariate analysis showed a strong association between HGCP and CC both and several preoperative and final pathology results, including digital rectal examination, pathology tumor stage, extraprostatic extension, surgical margin positivity, high Gleason sum (GS), and high tumor volume. Kaplan-Meier analysis showed HGCP to have a 61% cumulative prostate-specific antigen (PSA) failure rate in contrast with CC and pure acinar cancer, which had cumulative PSA failure rates of 15% and 13%, respectively (p = 0.0001, log-rank test). Multivariate Cox's proportional-hazards analysis found preoperative serum PSA, GS, tumor stage, and volume to be important predictors of PSA failure. In a second regression model that included serum PSA, GS, and pathology tumor stage, HGCP was an independent predictor of PSA failure. Both HGCP and CC are closely associated with several poor prognostic indicators, including advanced pathology tumor stage, a high GS, and serum PSA. Multivariate analysis showed HGCP as an independent prognostic indicator. The close association between high tumor volume and HGCP supports the theory that the development of HGCP is a late event in tumor progression, more compatible with the intraductal spread of tumor than dysplasia.
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PMID:Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications. 966 46


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