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Robert H Getzenberg

Publications and source records attributed to Robert H Getzenberg.

At least 19 recordsLinked to original sources
PubMed2007

A preliminary study of JM-27: a serum marker that can specifically identify men with symptomatic benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia is a common disease in men that until recently was considered a single disease with varying symptoms. Our recent analysis has revealed that a molecular marker, JM-27, is able to distinguish at the tissue level between highly symptomatic individuals and those with histological disease. The goal of these studies was to determine if a serum based assay to detect JM-27 could distinguish men with different forms of benign prostatic hyperplasia. MATERIALS AND METHODS: A serum based enzyme-linked immunosorbent assay was developed using a novel anti-JM-27 monoclonal antibody. The assay was sensitive, detecting JM-27 at the low ng/ml level within the serum. A quantitative measurement of serum JM-27 levels was performed in 68 patients. The patients consisted of 3 groups of 29 patients with asymptomatic benign prostatic hyperplasia (American Urological Association symptom score of 15 or less), 39 with symptomatic benign prostatic hyperplasia (American Urological Association symptom score 16 to 32) and 17 with confirmed prostate cancer. The assay cutoff was determined after a pilot run of samples and applied prospectively. RESULTS: Using the determined cutoff, serum levels of JM-27 can distinguish between symptomatic and asymptomatic patient sets. The sensitivity and specificity of the assay are 90% and 77%, respectively. The presence of prostate cancer in these men does not appear to alter the marker levels. CONCLUSIONS: The present study is believed to represent the first characterization of a serum based marker for severe benign prostatic hyperplasia.

Antigens, Neoplasm↗
PubMed2006

Urinary matrix metalloproteinase activity is not significantly altered in patients with renal cell carcinoma.

OBJECTIVES: Matrix metalloproteinases (MMPs) are proteins that degrade the extracellular matrix and have been shown to be elevated in the urine of patients with cancer. One action of MMPs is the degradation of collagen IV that plays a role in tumor invasion and metastasis. This degradation can be measured by a fluorescent microplate activity assay that has been suggested to identify patients with renal cell carcinoma (RCC). Our aim was to confirm the utility of urinary MMP activity as a diagnostic test for RCC. METHODS: Urine samples from 21 patients undergoing nephrectomy for renal masses, as well as from 2 patients undergoing retroperitoneal mass excision for presumed local recurrence, were collected. Urine samples from 47 healthy volunteers were also collected. After concentration, the urine samples were incubated with fluorescein-labeled collagen IV. The fluorescence activity in each sample was measured using a conventional fluorescent microplate reader to determine the degree of collagen IV degradation in each specimen. RESULTS: Of the 21 patients undergoing nephrectomy, 15 had RCC, and both patients undergoing retroperitoneal mass excision had pathologically confirmed RCC recurrence. The mean number of fluorescence units emitted from the urine of patients with RCC was 48,924 units (range 0 to 275,879). The mean number of fluorescence units emitted from the urine of healthy patients was 29,834 units (range 0 to 400,086). This difference was not statistically significant (P = 0.34). CONCLUSIONS: Despite previous evidence, urinary MMP activity was not an adequate test to identify RCC. Most normal urine samples had significant MMP activity.

Aged↗
PubMed2006

Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer.

Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression.

Adenocarcinoma↗
PubMed2006

Toward critical evaluation of the role(s) of molecular biomarkers in the management of bladder cancer.

Among genitourinary malignancies, bladder cancer is a common, potentially dangerous and exceedingly costly disease entity. Predicated on substantial gains in our understanding of the natural history and molecular biology of bladder cancer, recent years have seen an explosion of new applied technologies to aid clinicians in the management of bladder cancer. Herein we present a systematic overview of general conceptual issues and specific strategies of potential relevance to the clinical evaluation of patients with bladder cancer. A number of basic epidemiological issues provide the relevant background within which we should consider candidate biomarkers. Within this framework, we highlight a number of important recent research findings representative of the large number of candidate bladder cancer biomarkers that have emerged. With several markers already having obtained regulatory approval for clinical use, this topic is of clear relevance not only to researchers but also to the practicing physician. Bladder cancer is a common, costly, and potentially dangerous disease with the opportunity for significant technological inroads in the area of applied biomarkers. An appreciation of basic epidemiological considerations informs our consideration of the state of the art and identifies specific strategies amenable to further innovation.

Antibodies, Monoclonal↗
PubMed2006

Urinary markers in the detection of bladder cancer: what's new?

PURPOSE OF REVIEW: Bladder cancer is one of the most common genitourinary malignancies and is a potentially life-threatening diagnosis. For many patients, however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly, and invasive surveillance for recurrent and/or progressive disease. In the context of relative limitations of the current standard of cystoscopy and cytology, there has been burgeoning activity in the development of novel molecular urine-based markers for bladder cancer detection. RECENT FINDINGS: A large number of candidate bladder cancer biomarkers have emerged as our understanding of the molecular pathogenesis of the disease has evolved. Many of these are in the relatively earlier phases of development but several have received the approval of the United States Food and Drug Administration for clinical use and are already being applied to patients in clinical practice. SUMMARY: Urine-based markers for bladder cancer detection represent an area of substantial innovation and discovery with potentially profound scientific, clinical, and economic implications. As more of these tests become standardized and undergo evaluation in large multicenter trials, it is conceivable that a novel marker or panel of markers will emerge as a major enhancement to the current standard of care.

Biomarkers, Tumor↗
PubMed2005

Early molecular-level changes in rat bladder wall tissue following spinal cord injury.

Previously, we demonstrated using a rat model of spinal cord injury (SCI) that bladder wall tissue compliance significantly increased within the first 2 weeks following injury. In order to explore the potential molecular-level mechanisms of this event, the present study quantified molecules pertinent to bladder tissue remodeling and changes in mechanical properties. An initial gene array analysis followed by real-time qPCR revealed that the message levels for tropoelastin and lysyl oxidase were as high as 8-fold in SCI rats compared to normal. Furthermore, both the message and protein levels of TGF-beta1 and IGF-1, known stimulators of elastin synthesis, in SCI rat bladders were significantly higher compared to those of normal rats. Taken together, it can be speculated that functional changes of the bladder associated with SCI induce release of select growth factors, which, in turn, stimulate elastogenesis that lead to alteration of biomechanical properties of the wall tissue.

Adaptation, Physiological↗
PubMed2005

Mechanistic analysis of the role of BLCA-4 in bladder cancer pathobiology.

Analysis of alterations in nuclear structure associated with bladder cancer has revealed specific changes associated with the disease. This includes the identification of six bladder cancer-specific proteins and the successful development of urine-based immunoassays for the detection of two of these biomarkers, BLCA-1 and BLCA-4. The purpose of this study is to examine the functional aspects of BLCA-4 and its potential role in bladder cancer pathobiology. Sequence analysis of BLCA-4 reveals that it is a member of the ETS transcription factor family and that it seems to associate with transcription factors. To examine the effects of this protein, the gene encoding BLCA-4 was stably transfected into human urothelial cells. BLCA-4 expression was confirmed by both PCR and Western blot analysis. BLCA-4 overexpressing clones exhibit a 4.3-fold greater proliferation rate than vector only controls or untransfected cells. Microarray analysis comparing gene expression patterns between overexpressing clones and vector only controls revealed that numerous genes were up-regulated in cells that overexpress BLCA-4. Up-regulated genes included interleukin-1alpha (IL-1alpha), IL-8, and thrombomodulin, and the protein expression of these genes was confirmed by immunoblots. This information has provided a potential model of BLCA-4 action. Overexpression of BLCA-4 seems to increase the growth rate in cells and also causes cells to express a more tumorigenic phenotype.

Biomarkers, Tumor↗
PubMed2005

Detection of prostate cancer with a blood-based assay for early prostate cancer antigen.

Prostate-specific antigen lacks specificity for prostate cancer, so the identification and characterization of a unique blood-based marker for the disease would provide for a more accurate diagnosis, reducing both unnecessary biopsies and patient uncertainty. We previously identified a novel biomarker for prostate cancer, early prostate cancer antigen (EPCA). EPCA antibodies positively stained the negative biopsies of men who, as much as 5 years later, were diagnosed with prostate cancer. The goal of this study was to determine whether EPCA antibodies could be used in a clinically applicable plasma-based immunoassay to specifically detect prostate cancer. Using an EPCA-based ELISA, the protein was measured in the plasma of 46 individuals, including prostate cancer patients, healthy individuals, other cancer patients, spinal cord injury victims, and patients with prostatitis. With a predetermined cutoff value of 1.7 absorbance at 450 nm, only the prostate cancer population, as a whole, expressed plasma-EPCA levels above the cutoff. Statistical analysis showed a significant difference in EPCA levels between the prostate cancer population and each of the other groups, specifically the healthy donors (P < 0.0001), bladder cancer patients (P = 0.03), and spinal cord injury patients (P = 0.001). Sensitivity of the EPCA assay for prostate cancer patients was 92% whereas the overall specificity was 94%. Specificity for the healthy donors was 100%. Although larger trials are required, this initial study shows the potential of EPCA to serve as a highly specific blood-based marker for prostate cancer. EPCA, when coupled with prostate-specific antigen, may help reduce the number of both unnecessary biopsies and undetected prostate tumors.

Adult↗
PubMed2005

Efficacy of BTA stat, cytology, and survivin in bladder cancer surveillance over 5 years in patients with spinal cord injury.

OBJECTIVES: To evaluate three urine markers, BTA stat, cytology, and urinary survivin levels, in the spinal cord injury (SCI) population. The incidence of bladder cancer in patients with SCI is up to 20 times greater than in the general population. However, bladder cancer biomarkers have not been assessed in this population. METHODS: Between April 1999 and April 2004, 457 patients with SCI enrolled at the HealthSouth Harmarville Rehabilitation Spinal Cord Clinic donated their urine to our SCI urine repository. BTA stat tests and the survivin assay were performed according to published standards. Cytology specimens were sent to our cytopathology laboratory for analysis. RESULTS: A total of 1075 urine specimens from 457 patients were analyzed. Of the 1073 BTA stat tests, 119 showed positive reactions and 954 were negative. In the survivin assays, 47 samples had a score of 1, 38 a score of 2, and 9 a score of 3. No cytology specimens were noted to have malignant cells. During the past 5 years, 3 patients were diagnosed with bladder cancer by cystoscopy and treated for superficial disease. For these patients, none of these three tests (BTA stat, survivin assay, and cytology) was positive before the diagnosis of bladder cancer. CONCLUSIONS: The BTA stat, survivin assay, and urine cytology were unable to predict bladder cancer cases in our cohort of patients with SCI. Cystoscopy, therefore, remains the gold standard for bladder cancer surveillance in patients with SCI.

Biomarkers↗
PubMed2005

Highly specific urine-based marker of bladder cancer.

OBJECTIVES: Bladder cancer represents a major health problem throughout the world, but advances in tumor biomarker development are revolutionizing how physicians diagnose the disease. We previously used an indirect immunoassay to demonstrate that the bladder cancer specific biomarker, BLCA-4, is present in urine samples from patients with bladder cancer, but not in samples from healthy individuals. In this study, a sandwich immunoassay was used to measure BLCA-4 in urine samples from patient populations with various urologic conditions and healthy individuals. METHODS: Urine was collected from healthy individuals and from patients with bladder cancer, benign urologic conditions, or prostate cancer. BLCA-4 levels were evaluated by a sandwich immunoassay using two antibodies directed against distinct epitopes on BLCA-4. RESULTS: Using a prospectively determined cutoff of an absorbance unit (OD) of 0.04, 67 of the 75 samples from patients with bladder cancer were positive for BLCA-4, resulting in an assay sensitivity of 89%. Also, 62 of the 65 samples from individuals without bladder cancer were negative for BLCA-4, resulting in an assay specificity of 95%. CONCLUSIONS: The high sensitivity and specificity of the sandwich BLCA-4 immunoassay may allow for earlier detection and treatment of disease, thus greatly improving patient care.

Adult↗
PubMed2005

Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.

This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.

Biomarkers, Tumor↗
PubMed2005

Prognostic markers for bladder cancer: International Consensus Panel on bladder tumor markers.

The International Consensus Panel on cytology and bladder tumor markers evaluated markers that have the ability to predict tumor recurrence, progression, development of metastases, or response to therapy or patient survival. This article summarizes those findings. The panel mainly reviewed articles listed in PubMed on various prognostic indicators for bladder cancer. Based on these studies, most of which were case-control retrospective studies, various prognostic indicators were classified into 6 groups: (1) microsatellite-associated markers, (2) proto-oncogenes/oncogenes, (3) tumor suppressor genes, (4) cell cycle regulators, (5) angiogenesis-related factors, and (6) extracellular matrix adhesion molecules. The panel concluded that although certain markers, such as Ki-67 and p53, appear to be promising in predicting recurrence and progression of bladder cancer, the data are still heterogeneous. The panel recommends that identifying definitive criteria for test positivity, a clearly defined patient population, standardization of techniques used to evaluate markers, and clearly specified endpoints and statistical methods will help to bring accurate independent prognostic indicators into the clinical management of patients with bladder cancer.

Angiogenic Proteins↗
PubMed2005

Benign prostatic hyperplasia cell line viability and modulation of jm-27 by doxazosin and Ibuprofen.

PURPOSE: Benign prostatic hyperplasia (BPH) is among the most common diseases affecting quality of life in older men. Despise intense research efforts to our knowledge the genetic mechanisms underlying the BPH disease process and therapeutic markers needed to determine patient responsiveness to a particular form of pharmacological therapy are still not identified. This has slowed the development of new therapeutic agents for the treatment of BPH. MATERIALS AND METHODS: We investigated the cellular effects of certain drugs on BPH. Besides doxazosin, which is the prevailing drug to treat BPH, the effect of ibuprofen was examined as a new therapeutic approach due to strong evidence of a correlation between BPH and inflammation. RESULTS: This study showed that doxazosin as well as ibuprofen significantly decreases cell viability and induced apoptosis in 267 B1 cells as well as in BPH-1 cells. In addition, we observed that the administration of doxazosin and ibuprofen to BPH-1 cells decreased the expression of JM-27, a protein particularly expressed in prostate that is highly up-regulated in symptomatic BPH. CONCLUSIONS: Our findings suggest that ibuprofen may be a new therapeutic target for the treatment of BPH. Further research must be done to investigate the potential use of ibuprofen in patients with BPH and examine if JM-27 expression in patients with BPH may stratify individuals who may be most responsive to pharmacological treatment.

Adrenergic alpha-Antagonists↗
PubMed2005

Use of the novel marker BLCA-1 for the detection of bladder cancer.

PURPOSE: Bladder cancer specific nuclear structural alterations have been identified. We examined the expression pattern of one of these proteins, BLCA-1, in tissue and urine samples from individuals with bladder cancer as well as in samples from normal controls. MATERIALS AND METHODS: BLCA-1 sequence data were used to produce antibodies to this protein, which were used in immunoblot and enzyme-linked immunosorbent assays. RESULTS: BLCA-1 was detectable in tissue from patients with bladder cancer but not in normal adjacent areas of the bladder or in normal donor bladder tissue. This protein was also detectable in the urine of patients with bladder cancer by immunoblot and immunoassay. Using a cutoff of 0.025 optical density units (absorbance value) BLCA-1 was detected in 20 of 25 urine samples from patients with bladder cancer but in only 6 of 46 normal, high risk, prostate or renal cancer samples tested, resulting in a test with 80% sensitivity and 87% specificity. Expression of this protein did not appear to correlate with tumor grade. CONCLUSIONS: This research indicates that BLCA-1 is a urine based marker of bladder cancer which may be useful for the detection of this disease.

Adult↗
PubMed2005

Contribution of the prostate limits the usefulness of survivin for the detection of bladder cancer.

PURPOSE: We determined if urinary survivin is influenced by the prostate and analyzed survivin levels in a healthy control population. MATERIALS AND METHODS: This was a blinded, retrospective analysis of frozen urine samples. Three groups were designated. Group 1 patients were diagnosed with prostate cancer and samples were collected immediately prior to radical retropubic prostatectomy. Group 2 patients had already undergone radical retropubic prostatectomy at least 3 months prior to providing a urine sample. Group 3 comprised healthy controls. Groups 1 and 2 patients were recruited at an institutional practice. Group 3 patients were recruited from the local community. RESULTS: The frequency of high survivin scores was much lower in patients who did not have a prostate (p < 0.0002). The survivin score was 2 in 35% and 44% of the patients in groups 1 and 3, respectively, while only 9% of those in group 2 had a survivin score of 2 (p < 0.0002). Of healthy controls 50% had a false-positive survivin score. Urinary survivin predicted prostate cancer poorly with 52% sensitivity and 50% specificity, and it did not predict any biological features of prostate cancer. CONCLUSIONS: Urinary survivin markedly decreases after prostatectomy. There is a 50% false-positive rate when using urinary survivin in controls. These 2 features make urinary survivin a poor bladder cancer biomarker.

Aged↗
PubMed2005

Noninvasive testing for colorectal cancer: a review.

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Endoscopic screening is now in favor and its use is increasing, but overall participation rates are poor. A substantial percentage of the population will likely continue to resist endoscopic screening. As such, a noninvasive biomarker for the early detection of CRC remains a priority. Herein, we (i) review the currently available noninvasive screening markers for the early detection of CRC, (ii) discuss newer markers that have undergone preliminary testing, and (iii) introduce and explain potentially promising markers of the future. METHODS: The published literature on markers for early detection of CRC was identified using a MEDLINE/PubMed search with secondary review of cited publications. RESULTS: Noninvasive testing for CRC is most advanced in testing for stool fecal occult blood, globin, or DNA mutations. Study of abnormal mucins has also been explored. Research for serum-based markers is just beginning and includes serum proteomics, nuclear matrix proteins, and serum DNA testing. CONCLUSIONS: Serial guaiac-based fecal occult blood testing (FOBT) is simple, inexpensive, and proven effective at reducing mortality from CRC. Immunochemical fecal occult blood tests facilitate compliance and offer improved specificity, but at increased cost in comparison to FOBT. Fecal DNA testing may provide enhanced sensitivity for detection of CRC in comparison with FOBT, but its high cost limits its use for generalized screening. Rectal mucin testing requires additional evaluation to determine its sensitivity and specificity in comparison with guaiac-based FOBT. Serum tests, such as proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy, but remain a hope for the future.

Biomarkers, Tumor↗
PubMed2005

Androgens and prostate cancer: are the descriptors valid?

The term androgen-independent cancer has now become a misnomer. Given that the androgen receptor can be activated by even low androgen concentrations or via protein modifications or other protein-protein interactions, a growing prostate cancer has the chance of assuming an androgen depletion-independent state, without necessarily bypassing the androgen signaling processes. It is thus suggested that "androgen-independent (AI)" cancer should be more accurately termed "androgen depletion-independent (ADI)" cancer.

Androgen Antagonists↗