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 options available for patients with recurrent prostate cancer are limited. Men who have failed external-beam irradiation as the primary treatment are rarely considered for potentially curative salvage therapy. Traditionally, only palliative treatments have been offered with hormonal intervention or simple observation. A significant percentage of these patients have only locally recurrent cancer and are thus candidates for curative salvage therapy. Permanent brachytherapy with iodine-125 or palladium-103 has been used in an attempt to eradicate the remaining prostate cancer and prevent the need for additional intervention. It is critical in this population to identify patients most likely to have distant metastases or who are unlikely to suffer death or morbidity from their recurrence, in order to avoid potential treatment morbidity in those unlikely to benefit from any intervention. Following salvage brachytherapy, up to 98% of these cancers may be locally controlled, and 5-year freedom from second relapse is approximately 50%. With careful case selection, relapse-free rates up to 83% may be achieved. A schema is presented, suggesting that it may be possible to identify the patients most likely to benefit from salvage treatment based on prostate-specific antigen (PSA) kinetics and other features. Such features include histologically confirmed local recurrence, clinical and radiologic evidence of no distant disease, adequate urinary function, age, and overall health indicative of at least a 5- to 10-year life expectancy, prolonged disease-free interval (> 2 years), slow PSA doubling time, Gleason sum < or = 6, and PSA < 10 ng/mL.
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PMID:Salvage brachytherapy after external-beam irradiation for prostate cancer. 1500 55

Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) are important multifunctional cytokines involved in tumour growth and metastasis. In this study, we have measured serial levels of serum IL-6 and TNF-alpha in prostate cancer patients. A total of 80 patients with carcinoma of the prostate and 38 controls were studied. Three patient groups, with small bulk localised, large volume localised and metastatic prostate cancer, were assessed. Serum IL-6 and TNF-alpha levels were measured and correlated with clinicopathological variables and patient survival. Serial changes in these cytokines were also assessed and related to disease progression in 40 patients with recurrent prostate cancer. Serum IL-6 levels in patients with metastatic disease (9.3+/-7.8 pg x ml(-1)) were higher than those in patients with localised disease (1.3+/-0.8 pg x ml(-1), P<0.001). Significantly elevated levels of TNF-alpha were found in metastatic disease (6.3+/-3.6 pg x ml(-1)) compared with localised disease (1.1+/-0.5 pg x ml(-1), P<0.001). The levels of both cytokines were directly correlated with the extent of the disease. Serial analysis in 40 patients with recurrent tumours showed that both cytokines became elevated at the point of prostate-specific antigen progression. In conclusion, these results suggest that IL-6 and TNF-alpha correlate with the extent of disease in patients with prostate cancer and may be monitored in conjunction with other disease markers.
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PMID:Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. 1515 May 88

Institutional review board approval and written informed consent were obtained. Patients with newly diagnosed prostate cancer and patients suspected of having recurrent prostate cancer were prospectively evaluated with fluorine 18 fluorocholine (FCH) combined in-line positron emission tomography (PET) and computed tomography (CT). In 19 patients (mean age, 67 years +/- 8; range, 57-85 years), standardized uptake values of FCH in 17 different tissues were determined by using volumes of interest. In nine patients evaluated at initial staging, histologic findings of the resected prostate were compared to FCH uptake. Only small variations of physiologic tracer accumulation were measured in all organs but the kidneys. Differentiation of benign hyperplasia from cancerous prostate lesions was not possible with FCH PET/CT. However, in patients with recurrent prostate cancer, FCH PET/CT is a promising imaging modality for detecting local recurrence and lymph node metastases.
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PMID:Fluorocholine PET/CT in patients with prostate cancer: initial experience. 1585 2

Prostate cancer is a leading cause of cancer death in men. Risk prognostication, treatment stratification, and the development of rational therapeutic strategies lag because the molecular mechanisms underlying the initiation and progression from primary to metastatic disease are unknown. Multiple lines of evidence now suggest that KLF6 is a key prostate cancer tumor suppressor gene including loss and/or mutation in prostate cancer tumors and cell lines and decreased KLF6 expression levels in recurrent prostate cancer samples. Most recently, we identified a common KLF6 germ line single nucleotide polymorphism that is associated with an increased relative risk of prostate cancer and the increased production of three alternatively spliced, dominant-negative KLF6 isoforms. Here we show that although wild-type KLF6 (wtKLF6) acts as a classic tumor suppressor, the single nucleotide polymorphism-increased splice isoform, KLF6 SV1, displays a markedly opposite effect on cell proliferation, colony formation, and invasion. In addition, whereas wtKLF6 knockdown increases tumor growth in nude mice >2-fold, short interfering RNA-mediated KLF6 SV1 inhibition reduces growth by approximately 50% and decreases the expression of a number of growth- and angiogenesis-related proteins. Together, these findings begin to highlight a dynamic and functional antagonism between wtKLF6 and its splice variant KLF6 SV1 in tumor growth and dissemination.
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PMID:Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread. 1599 51

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.
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PMID:Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer. 1656 29

The importance of androgens and androgen receptors (AR) in primary prostate cancer is well established. Metastatic disease is usually treated with some form of androgen ablation, which is effective for a limited amount of time. The role of AR in prostate cancers that recur despite androgen ablation therapy is less certain. Most of these tumors express prostate specific antigen (PSA), an androgen-regulated gene; moreover, AR is generally highly expressed in recurrent prostate cancer. We propose that AR continues to play a role in many of these tumors and that it is not only the levels of AR, ligands, and co-regulators, but also the changes in cell signaling that induce AR action in recurrent prostate cancer. These pathways are, therefore, potential therapeutic targets.
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PMID:Androgen receptor action in hormone-dependent and recurrent prostate cancer. 1661 64

We present a retrospective study to evaluate the outcome of postoperative radiotherapy for biochemical or clinical recurrent prostate cancer. Twenty-six patients (median age 60 years) underwent radiotherapy after radical prostatectomy between January 1997 and January 2004. Seven patients received adjuvant radiotherapy and 19 received salvage radiotherapy. The median prostate-specific antigen at diagnosis was 8.6 (0.9-89) and most (23 patients) presented with T(3)N(0) disease. The median follow up was 19.5 months (5-84 months). All patients received a dose of 61.2 Gy at 1.8 Gy per fraction, 20 initially receiving 45 Gy to the lesser pelvis. The median dose to the bladder, rectum and left femoral head were 55.6, 57.5 and 33.8 Gy, respectively. All patients were managed radiotherapeutically by the first author. Twenty-four patients are alive. Two patients have died, one from oesophageal cancer and the second from metastatic prostate cancer. Two other patients also developed metastatic disease. Four asymptomatic patients with a rising prostate-specific antigen are under observation. None of the 26 patients has developed a local recurrence. Seven patients have developed grade 1 late bowel effects and three a grade 2 late effect. Eight patients suffer from grade 1 late genitourinary effects and two from grade 2 effects. One patient developed impotence, whereas 23 patients were rendered impotent postoperatively. There were no grade 3/4 late effects. Postoperative radiotherapy is well tolerated and provides effective local control.
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PMID:Outcome of post-prostatectomy radiotherapy in one institution. 1698 46

The presentations for the "Advanced Disease" section of the 13th International Prostate Cancer Update provided an overview of current and future directions in the management of men with recurrent prostate cancer after local therapy and those with metastatic disease. Definitions of biochemical failure after local therapy were reviewed. Treatment strategies that were discussed included salvage radiation, early/intermittent hormonal therapy, cytotoxic chemotherapy, the use of bisphosphonates, and gene therapy. Several possible molecular targets for prostate cancer treatment need further validation before testing in clinical trials, and examples of these were presented. Each presentation focused on the need to accrue men to clinical trials to enable progress at a faster pace.
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PMID:Prostate cancer update: advanced disease. 1698 77

Each year, approximately 210,000 American men are diagnosed with prostate cancer and 41,800 die from the disease - numbers roughly equal to the incidence and mortality for breast cancer in women. Prostate cancer usually shows no symptoms in early stages, when it is most treatable. To detect the disease early, physicians usually recommend that every man 50 years and older have an annual examination consisting of a digital rectal examination and a prostate specific antigen (PSA) blood test. Conventional treatments such as surgical removal of the diseased prostate, external beam radiation, radioactive seed therapy and hormonal and/or chemotherapy treatment regimens are most successful for early stage prostate cancer and have limited effectiveness in advanced stages of the disease. For this reason, accurate staging of primary and recurrent prostate cancer is mandatory for proper therapeutic decisions. Nuclear medicine imaging of prostate cancer using the radiolabelled monoclonal antibody, (111)In-capromab pendetide, has proven useful in newly diagnosed patients with biopsy-proven prostate cancer in which there is high suspicion of distant metastatic disease and for prostatectomy patients with rising PSA levels and/or suspicion of recurrence or metastatic disease. Although not intended as a screening tool, it is used in conjunction with standard evaluation procedures for improved staging of patients. The monoclonal antibody, designated 7E11-C5, binds the prostate specific membrane antigen (PSMA) expressed on the surface of prostate epithelial cells and up-regulated in tumour cells. The sensitivity and specificity for prostate cancer involved lymph node detection has been reported as 62 to 75% and 72 to 86%, respectively, compared with sensitivities of 4% and 15% for computerised tomography and magnetic resonance imaging. (111)In-capromab pendetide imaging has proven to be an accurate, non-invasive tool for detecting and staging sites of recurrence in the post-prostatectomy patient as well as metastatic sites in the patient with newly diagnosed prostate cancer.
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PMID:111In-capromab pendetide: the evolution of prostate specific membrane antigen and the nuclear imaging of its 111In-labelled murine antibody in the evaluation of prostate cancer. 1803 50

Locally recurrent prostate cancer can lead to significant morbidity, metastasis, and even death. The objective of this study was to evaluate the efficacy of an injectable polymeric paste formulation containing paclitaxel against orthotopic prostate tumor in rats. The Dunning R-3327 rat prostate adenocarcinoma is experimental tumor model used to study tumor progression. The polymer loaded with paclitaxel was injected into the tumor bearing prostate glands of the rats 3 days after tumor cell inoculation. In control untreated rats, tumor volume reached 14 cm(3) after 25 days, while in rats treated with intratumoral injection of polymer/paclitaxel formulation the prostate volume with the tumor was only 0.9 cm(3), 35 days posttumor cells inoculation. In the group treated with intratumoral injection of paclitaxel suspension, the tumor volume was 6.6 cm(3), and in the group treated with intraperitonial (IP) paclitaxel formulation, the tumor volume reached 13.9 cm(3) 25 days posttumor cells inoculation. No metastases were found in rats treated intratumorally with 200 microL of polymer/paclitaxel formulation, while rats in other treatment groups developed metastases in the lungs and lymph nodes. The results of this study indicated that a site-directed, injectable, controlled release formulation of paclitaxel is effective against localized prostate tumors and metastasis.
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PMID:Intratumoral delivery of paclitaxel for treatment of orthotopic prostate cancer. 1866 40


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