Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.
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PMID:Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor. 128 86

Unknown primary malignancy (UPM) is not a disease entity. Rather, it represents a variety of different metastatic, malignant neoplasms all presenting with either an occult primary or having such a highly undifferentiated histologic appearance that an accurate pathologic classification on routine hematoxylin-eosin section is not possible. UPM is a spectrum of malignancies that includes those that are treatable and curable and those for which no specific treatment exists. For the physician, a diagnosis of UPM represents a beginning rather than an end. The minimal workup of such patients includes a thorough history and physical examination, complete blood counts, urine analysis, multichannel chemistries, a chest radiograph, and computed tomography of the abdomen and pelvis. Having completed this workup, further tests are unnecessary and unwarranted unless specific symptoms or physical signs exist. Once the aforementioned workup is completed, the physician must communicate frequently and freely with the pathologist as further diagnostic tests will be laboratory based and include electron microscopy, histochemical stains, and immunocytochemistries. Immunocytochemistries are relatively new laboratory procedures which have made a significant contribution in the accurate pathologic diagnosis of a tissue specimen that in years past would have been classified as an unidentified malignant neoplasm. An initial panel of immunocytochemistries (vimentin, cytokeratin, CEA, and common leukocyte antigen) should be performed on the tissue block in patients with UPM as they provide direction in the accurate classification of the malignant neoplasm. Chromosomal analysis of tissue is useful in the recognition of lymphomas or soft-tissue sarcomas which would otherwise be classified as UPM. In years to come, when specific DNA probes capable of identifying specific chromosomal rearrangeaments are widely available, pathologic classification of UPM will be performed on a molecular level. Some unknown primary malignancies are treatable and potentially curable. These include large cell lymphoma, extragonadal germ cell malignancies, squamous cell carcinoma metastatic to cervical lymph nodes without an obvious primary, metastatic adenocarcinoma to axillary lymph nodes in women (invariably on occult breast primary), and malignant ascites in women, which usually represents ovarian cancer. Metastatic adenocarcinoma of unknown primary origin, with the exception noted above and the rare presentation of an occult prostate cancer as UPM, is an ultimately fatal malignancy with a relatively shor clinical course.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Malignancies of undetermined primary origin. 154 98

In an effort to better distinguish the morphologic relationship of atypical hyperplasia of the prostate to benign prostatic hypertrophy and prostatic cancer, 43 prostate specimens were analyzed with ten immunohistologic markers. Two cytokeratin antibodies appeared useful (Cyto M and Cyto P, with the latter slightly more discriminatory). In summary, it appears that atypical hyperplasia is immunohistopathologically related to both benign prostatic hypertrophy and prostatic cancer, having characteristics of both.
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PMID:An immunohistologic characterization of human prostatic atypical hyperplasia. 169 11

The purpose of the present study was to identify cytokeratin polypeptides that are specifically associated with the basal and luminal epithelia of the human prostate. This aim was accomplished by immunohistochemical and immunoblot analysis of human prostate using cytokeratin-specific monoclonal antibodies. In immunohistochemical studies, monoclonal anticytokeratin 8.12 exhibited immunoreactivity with the basal, but not luminal, epithelial cells of fetal, juvenile, normal adult, and hyperplastic prostate. The 8.12 antibody did not stain prostate cancer tissues. Epithelia of 30 and 36 week fetal prostate contained only basal cells whereas both luminal and basal cells were noted in 7 month and 1 year old juvenile prostate. This finding suggests a stem cell function for the prostatic basal cells. Immunoblot analysis of proteins separated by two-dimensional electrophoresis showed that cytokeratins 5 and 15 were basal-cell-specific cytokeratins that were absent from prostatic carcinoma while cytokeratins 8 and 18 appear to be luminal-cell-specific. These results indicate that antibodies to specific cytokeratin polypeptides can be used not only to differentiate between prostatic basal and luminal cells but also to study the biological processes of prostatic organogenesis and carcinogenesis.
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PMID:Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate. 171 87

Florid basal cell hyperplasia of the prostate is an uncommon proliferative condition, most often associated with adenomatous hyperplasia. It is considered a benign lesion although confusion with prostatic cancer is possible when one is not familiar with the histopathological appearance. We report another two cases of the glandular type of basal cell hyperplasia with immunohistochemical findings. Both lesions were composed of crowded and rather small glands with piling up of basaloid cells. They showed immunohistochemical positivity for high molecular weight cytokeratin 34 beta E12, confirming their relationship with basal cells. We detected focal positivity of these basal cells for alpha-smooth muscle actin, suggesting myoepithelial differentiation. Paucity of actin-positive smooth muscle cells in the stroma was noticed. One of the lesions showed some mild cytological atypia with prominent nucleoli and increased mitotic activity.
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PMID:Florid basal cell hyperplasia of the prostate. 751 64

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+ cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+ tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer. 752 Oct 88

Serum tissue polypeptide-specific antigen (TPS), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) concentrations were serially measured in 31 prostate cancer patients with bone metastases who had relapsed following hormonal therapy. Of these subjects 7 had well-differentiated cancer (G1), 13 patients were assessed to have moderately differentiated tumor (G2) while in 11 subjects poorly differentiated tumor (C13) was found. With increasing tumor grade (G1 to G3), a proportional increase in mean TPS value was found while the increase in respective PAP serotest values was not linear. Simultaneously measured mean PSA values showed a curved effect. Both PSA and PAP serotest concentrations depend on the respective hormone-dependent gene expressions that gradually decrease with tumor dedifferentiation. Therefore, in progressive hormonally treated stage D2 prostate cancer patients an androgen-independent TPS serotest seems to be a useful clinical addition for monitoring protocols. The combined use of TPS, PSA, and PAP seems to give a better reflection of tumor status. According to the bone scan data metastatic tumor mass in G3 carcinomas was virtually equal to cancer burden in G2 tumors. Hence, the marked elevation of TPS serotest values in G3 adenocarcinomas could not be attributed to greater tumor mass but was most likely due to an increase in proliferation rate. Some authors have recently proposed cytokeratins 8, 18, and 19 to be the origin of TPS serum findings. However, cytokeratin content has been proven to be lower in G3 tumors than in better-differentiated neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum TPS, PSA, and PAP values in relapsing stage D2 adenocarcinoma of the prostate. 753 45

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumour cells. 768 10

c-erb B2/neu has been demonstrated to be a transforming oncogene in both rodent and human prostatic epithelial cells. To understand the potential role of neu in human prostatic cancer progression, we used a transfer procedure to determine whether neu amplification/overexpression leads to increased tumor growth and metastasis. We chose an androgen-independent human prostatic epithelial cell line, PC-3, as the target for gene transfer. PC-3 cells were cotransfected with pSVneu-T (a point-mutated rat neu oncogene construct) and pSV2neo, and single-cell cloned. Fifty cell clones were isolated and characterized, of which two neu-transfected clones (N17 and N35) and a neo control clone (C32) were studied extensively with respect to neu gene integration, levels of neu mRNA and protein expression, anchorage-independent growth, and tumorigenic and metastatic potential. Results showed that: 1) Clone N35 contained 70 copies of the neu oncogene and a high level of neu mRNA transcripts. It acquired increased anchorage-independent growth potential in vitro and increased tumorigenicity in vivo. 2) Clone N17 contained 10 copies of the neu oncogene and a low level of neu mRNA transcripts. It did not acquire additional capability for anchorage-independent growth and tumorigenic potential as compared to the controls. 3) Despite an increased level of neu mRNA transcripts present in clone N35, there was no corresponding increase of the steady-state levels of neu protein in this particular clone. 4) When administered subcutaneously, none of the cell clones tested, including the control neomycin-resistant clone, acquired metastatic potential. However, clone N35 exhibited marked metastatic potential when administered orthotopically; this cell clone was found to disseminate widely to the lymph nodes, kidney, skeletal muscle, lung, liver, and bone. 5) When neu-transfected cell subclones from N35-induced primary and metastatic lymph node, kidney, and bone tumors were analyzed for cytoskeletal, extracellular matrix, and cell adhesion protein expression, the bone metastatic subclone exhibited increased levels of vimentin and collagen IV and decreased levels of cytokeratin and ICAM-1. These results, taken together, suggest that neu transfection induces secondary changes, which, rather than neu protein per se, are responsible for the acquisition of tumorigenic and metastatic potential of prostate cancer cells when an appropriate host microenvironment is present.
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PMID:Transfected neu oncogene induces human prostate cancer metastasis. 860 95

Up to 60% of patients with clinically localized prostate cancer will relapse despite potentially curative local treatment. Current staging tests have been limited in adequately identifying individual patients who are at a high risk for future relapse. Detection of bone marrow micrometastases may identify individuals destined to develop clinically detectable systemic metastases. Although immunohistochemistry and molecular approaches are being investigated, the most ideal test(s) are yet to be determined. In this report we describe methods for specific detection and isolation of prostate cancer micrometastases by multi-parameter rare event flow cytometric analysis. A model was developed and validated using three human prostate cancer cell lines, healthy donor marrow, dual marker labeling for cytokeratin (epithelial-specific marker) and CD45 (bone marrow-specific marker). The detection sensitivity of this model was at the level of one prostate cancer cell in 100,000 nucleated bone marrow cells. As a part of an ongoing clinical study, bone marrow aspirates from 15 patients with newly diagnosed prostate cancer have been analyzed. Six patients were found to have cytokeratin positive/CD45 negative cells in their bone marrow aspirates. We conclude that flow cytometric rare event analysis provides a sensitive and specific assay for detection of bone marrow micrometastases in patients with clinically localized prostate cancer.
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PMID:Prostate cancer: flow cytometric methods for detection of bone marrow micrometastases. 880 79


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