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)

Chromogranin A is a cellular marker forneuroendocrine tumors. Elevated levels of chromogranin A are also found in patients with cancers of epithelial origin when neuroendocrine differentiation occurs, which is associated with a poor prognosis. We investigated the prevalence of serum levels of chromogranin A in patients with primary liver cancer. Seventy-nine patients (65 males, mean age 67.6 years, range 48-88 years) with liver cirrhosis and hepatocellular carcinoma were studied. The etiology of cirrhosis was identified as due to hepatitis C virus infection in 47 patients, to hepatitis C virus and alcohol in 7, to alcohol alone in 14, to hepatitis C and B virus in 2, and to hepatitis B virus alone in 4. Of the remaining patients, 2 suffered from hemochromatosis and 3 had cryptogenic cirrhosis. According to the Child-Pugh's score, 54 patients belonged to class A, 22 to class B, and 3 to class C. The concentration of chromogranin A was measured in serum with a commercial solid-phase two-site immunoradiometric assay. Elevated serum levels of chromogranin A were found in 32 of 79 patients (43%). Levels over 600 ng/ml were present in 7 of 76 patients (9.2%), all of whom had very high serum levels of alpha-fetoprotein. Hence, elevated serum levels of chromogranin A are present in over one third of patients with hepatocellular carcinoma. It is therefore possible that some hepatocellular carcinomas could acquire a neuroendocrine differentiation. We propose further studies to ascertain whether serum levels of chromogranin A are useful as a prognostic marker for hepatocellular carcinoma as in prostate cancer.
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PMID:Elevated serum chromogranin A in patients with hepatocellular carcinoma. 1244 8

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non-epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (epsilon(0) approximately 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP.
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PMID:Photodynamic therapy with Pd-Bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts. 1264 Jun 88

The incidence of prostate cancer is remarkably increased in the last decade. This dramatic epidemiological change can be primarily attributed to the widespread use of prostate specific antigen (PSA) as a diagnostic tool. Nowadays most of the prostate cancers are detected at an early stage and the age of the patients is decreased. This has led to a significantly increase in the number of prostate cancer patients treated by radical prostatectomy. Serum determination of PSA is the standard method to monitor the disease after radical surgery, while other tests can be required only when PSA is detectable. After radical prostatectomy the mean half-life of PSA is 1.5 days and it must become undetectable to consider a patient free of disease. A value greater than 0.4 ng/ml, with an increase in two determination, indicates a recurrence of the disease. PSA is an extremely sensitive marker. In fact, in patients who underwent radical prostatectomy, the presence of detectable serum PSA levels allows to detect tumor recurrence even before any other diagnostic investigation (radiological or scintigraphical) becomes able to document it ("serological" disease). Unfortunately, increasing serum PSA levels do not reveal whether a patient is affected by local relapse or by metastases, with obvious repercussion for the therapeutic choice. Clinical examination of the patient, together with random and echoguided biopsies of the vesico-urethral anastomosis, do not reveal all cases of local recurrence. Ongoing study are evaluating other diagnostic tools in the monitoring patients after radical prostatectomy, such as the serum chromogranin A, the reverse transcriptase-polymerase chain reaction for PSA and prostate specific membrane antigen (PSMA), the Positron Emission Tomography and the immunoscintigraphy with radiolabeled monoclonal antibody directed toward the PSMA.
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PMID:[Clinical surveillance after surgery for prostate cancer]. 1267 77

The normal prostate shows a high degree of cellular organization. The basal layer is populated by prostate epithelial stem cells and a population of transiently proliferating/amplifying (TP/A) cells intermediate to the stem cells and fully differentiated cells. The luminal layer is composed of fully differentiated prostate epithelial cells. Neuroendocrine cells are scattered throughout the gland. This organization is also seen in prostate cancer, where the tumor cell origin (cancer stem cells) can be traced to a normal cell type by characteristic keratin expression patterns. Basal cells showed strong expression of K-[keratin]5, but they were only weakly positive for K18. Luminal cells strongly expressed K18. A subpopulation of basal cells coexpressed K5 and K14. These keratin expression patterns changed with the degree of cell differentiation as well as location. The least differentiated stem cells in the basal layer were positive for K5 and K14, with weak expression for K18. Intermediate stages of differentiation were identified by expression of K5 and K18. Neuroendocrine cells also expressed K5 as well as typical neuroendocrine cell markers (eg, chromogranin A). Evidence supporting the hypothesis that prostate cancer arises from malignant transformation of intermediate stem cells included the presence in prostate cancers of keratin patterns associated with the intermediate stages of differentiation, androgen independence of both prostate cancers and intermediate stem cells, and expression of c-met by both the TP/A intermediate stem cells and tumor cells.
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PMID:Cellular and molecular biology of the prostate: stem cell biology. 1460 13

The aim of this study was to investigate whether there is an association between the presence of neuroendocrine elements in relapsed prostate cancer and sensitivity to estramustine/etoposide and carboplatin or cisplatin. Thirty patients with progressive metastatic castrate prostate cancer were selected on the basis of clinical criteria for treatment with cytotoxic chemotherapy. The criteria included a tumor biopsy specimen taken during relapse showing neuroendocrine features based on morphology alone (carcinoid elements, small cell tumor) or by immunohistochemistry (detection of chromogranin A, neuron-specific enolase or synaptophysin). Patients were treated with cis- or carboplatin, estramustine (orally) and etoposide (orally or intravenously). Remission of radiographically visualized lesions, decline of prostate-specific antigen (PSA) or death owing to any cause constituted (separately reported) the endpoints. Tumor remission was found in about half of the patients, determined either by changes in measurable lesions or by a 50% decline in serum PSA. Neuroendocrine elements--irrespective of how they were identified--were not predictive of tumor remission or survival. Regression of measurable lesions by > 50% was seen in 4/9 (44%) cases of small cell carcinoma, 6/13 (46%) of poorly differentiated carcinoma, 7/13 (54%) of tumors with one marker immunohistochemically detected and 3/7 (43%) of tumors without any staining. It is concluded that response to chemotherapy was not predicted solely on the basis of the presence or absence of neuroendocrine elements in a relapsed tumor specimen. The results support the use of cytotoxic drugs in the relapsed setting and definitive trials are ongoing to prove any benefit to survival.
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PMID:Cytotoxic treatment of aggressive prostate tumors with or without neuroendocrine elements. 1465 Dec 12

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has attracted increasing attention in contemporary prostate cancer research. This particular phenotype, however, usually escapes pathological and clinical detection in routine practice. The present review focuses on the biological properties of NE tumor cells that make them resistant to androgen deprivation and radiation therapy. NE cells produce a number of hormonal growth factors (e.g., serotonin) that may act through endocrine, paracrine, and autocrine mechanisms. Morphogenetic studies have identified intermediate phenotypes between the three basic cell types of the prostatic epithelium indicating their common origin from stem cells located in the basal cell layer. Virtually all prostatic adenocarcinomas show NE differentiation as defined by the most commonly used endocrine marker chromogranin A. Clinical studies suggest that the extent of NE differentiation increases with tumor progression and the development of androgen insensitivity. NE differentiation exclusively occurs in the G0 phase of the cell cycle in which tumor cells are usually resistant to radiation therapy and cytotoxic drugs. In addition, NE tumor cells also escape programmed cell death. Even under androgen deprivation, only 0.16% of NE tumor cells show apoptotic activity. This indicates that the vast majority of NE tumor cells represent an immortal cell population in prostate cancer. Although NE tumor cells do not proliferate, they produce a number of NE growth factors with mitogenic properties that maintain cell proliferation in adjacent (exocrine) tumor cells through a paracrine mechanism. NE tumor cells consistently lack the androgen receptor and are androgen insensitive in all stages of the disease. They derive through a process of intermediate differentiation from exocrine tumor cells, the most prevalent phenotype in common prostatic adenocarcinoma. Elevated serum levels of chromogranin A in prostate cancer patients correlate with poor prognosis and are scarcely influenced by either androgen deprivation or chemotherapy. Looking for NE differentiation is recommended in the pathological and clinical evaluation of prostate cancer patients for whom radiation and androgen deprivation are therapeutic options.
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PMID:[Neuroendocrine differentiation in prostate cancer. An unrecognized and therapy-resistant phenotype]. 1504 55

The clinical and pathological features of metastatic prostate cancer with normal level of serum prostate-specific antigen (PSA) were investigated. Four patients with metastatic prostate cancer had serum PSA within the normal range at the diagnosis. All tumors were poorly-differentiated adenocarcinoma. Endocrine therapy was performed as the initial therapy in all patients. Despite subsequently treatment, all cases died of prostate cancer at 2, 8, 9 and 38 months. During disease progression, 3 of 4 patients had elevated serum markers such as carcinoembryonic antigen (CEA), CA19-9, CA15-3, CA125, neuron-specific enolase and pro-gastrin releasing peptide. Immunohistochemical examination of the initial biopsy specimens revealed that 4 and 3 cases were positive for CEA and chromogranin A, respectively. In advanced prostate cancer patients with low PSA level, those markers may aid in the follow up of disease.
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PMID:Metastatic prostate cancer with normal level of serum prostate-specific antigen. 1507 91

Neuroendocrine cells have been found in all the stages of prostate cancer, but their clinical significance is not completely understood. Neuroendocrine cells are androgen receptor- and prostate-specific antigen-negative, do not proliferate, and secrete many neuropeptides, such as chromogranin A. Neuroendocrine differentiation of prostate cancer correlates with an advancing tumour stage, poor prognosis and tumour progression after androgen deprivation. Furthermore, neuroendocrine phenotype is associated with the increased expression of neo-angiogenesis and vascular endothelial growth factor and with an over-expression of survivin, a new anti-apoptosis protein. Chromogranin A is the quantitatively major secretory protein of the vesicles inside neuroendocrine prostate cells and it is the marker most frequently used to detect neuroendocrine features, both in tissues and in general circulation. Tumours displaying neuroendocrine phenotype tend to be more aggressive and resistant to hormone-therapy. Neuroendocrine differentiation seems to be a dynamic phenomenon: in vitro and in vivo data suggest that it can be induced by androgen suppression. Moreover, the differences in the expression of somatostatin receptors between primary and hormone-refractory prostate cancer are likely to be related to the changes in neuroendocrine phenotype during androgen deprivation. Circulating chromogranin A levels seem to be scarcely affected by endocrine- and chemotherapy, while they significantly decreased after treatment with somatostatin analogs.
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PMID:Somatostatin receptors: from basic science to clinical approach. Unlabeled somatostatin analogues-1: Prostate cancer. 1507 13

Carcinoma of the prostate is the second leading cause of male cancer-related death in the United States. Better indicators of prostate cancer presence and progression are needed to avoid unnecessary treatment, predict disease course, and develop more effective therapy. Numerous molecular markers have been described in human serum, urine, seminal fluid, and histological specimens that exhibit varying capacities to detect prostate cancer and predict disease course. However, to date, few of these markers have been adequately validated for clinical use. The purpose of this review is to examine the current status of these markers in prostate cancer and to assess the diagnostic potential for future markers from identified genes and molecules that display loss, mutation, or alteration in expression between tumor and normal prostate tissues. In this review we cite 91 molecular markers that display some level of correlation with prostate cancer presence, disease progression, cancer recurrence, prediction of response to therapy, and/or disease-free survival. We suggest criteria to consider when selecting a marker for further development as a clinical tool and discuss five examples of markers (chromogranin A, glutathione S-transferase pi 1, prostate stem cell antigen, prostate-specific membrane antigen, and telomerase reverse transcriptase) that fulfill some of these criteria. Finally, we discuss how to conduct evaluations of candidate prostate cancer markers and some of the issues involved in the validation process.
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PMID:Detection of prostate cancer and predicting progression: current and future diagnostic markers. 1521 24

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
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PMID:Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. 1578 43


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