Biomedical subjects

S C Campbell

Publications and source records attributed to S C Campbell.

At least 19 recordsLinked to original sources

PubMed2006

Nitric oxide stimulates insulin gene transcription in pancreatic beta-cells.

Recent studies have identified a positive role for nitric oxide (NO) in the regulation of pancreatic beta-cell function. The aim of this study was to determine the effects of short-term exposure to NO on beta-cell gene expression and the activity of the transcription factor PDX-1. NO stimulated the activity of the insulin gene promoter in Min6 beta-cells and endogenous insulin mRNA levels in both Min6 and isolated islets of Langerhans. Addition of wortmannin prior to NO stimulation blocked the observed increases in insulin gene promoter activity. Although NO addition stimulated the phosphorylation of p38, inhibition by SB203580 did not block the effect of NO on the insulin gene promoter. NO addition also stimulated both the nuclear accumulation and the DNA binding activity of PDX-1. This study has shown that over 24h, NO stimulates insulin gene expression, PI-3-kinase activity and the activity of the critical beta-cell transcription factor PDX-1.

Androstadienes↗

PubMed2006

Androgen receptor levels are increased by interferons in human prostate stromal and epithelial cells.

Proliferation of normal and malignant prostate epithelium is regulated by androgen stimulation via both the androgen receptor (AR)-positive stromal and epithelial cells. However, it is not known how AR expression is regulated in human prostate cells. We report that treatment of normal human prostate stromal cells (PrSCs) with type I IFN (alpha or beta), but not type II IFN (gamma), resulted in increased levels of AR protein. The maximal increase in AR protein levels was dependent on the dose and the duration of the IFN-alpha treatment. We found that the increase in AR protein levels was independent of de novo transcription and protein synthesis. Interestingly, the IFN-alpha treatment of PrSCs resulted in considerable nuclear accumulation of AR, stimulation of AR-mediated transcription of reporter genes, and retardation of cell proliferation. Furthermore, treatment of normal human prostate epithelial cells with IFNs (alpha, beta or gamma) also resulted in increased levels of AR protein. Together, our observations identify the androgen receptor as an IFN-regulated protein in normal human prostate stromal and epithelial cells and predict that IFN-induced levels of AR in prostate cells contribute to the regulation of androgen signaling.

Adult↗

PubMed2006

Effects of rosiglitazone and metformin on pancreatic beta cell gene expression.

AIMS/HYPOTHESIS: Rosiglitazone and metformin are two oral antihyperglycaemic drugs used to treat type 2 diabetes. While both drugs have been shown to improve insulin-sensitive glucose uptake, the direct effects of these drugs on pancreatic beta cells is only now beginning to be clarified. The aim of the present study was to determine the direct effects of these agents on beta cell gene expression. METHODS: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6. Western blot and gel retardation analyses were used to examine the effects of both drugs on the regulation of IPF1 protein production, nuclear accumulation and DNA binding activity in both Min6 cells and isolated rat islets of Langerhans. RESULTS: Over 24 h, rosiglitazone promoted the nuclear accumulation of IPF1 and forkhead homeobox A2 (FOXA2), independently of glucose concentration, and stimulated a two-fold increase in the activity of the Ipf1 gene promoter (p<0.01). Stimulation of the Ipf1 promoter by rosiglitazone was unaffected by the presence of the peroxisome proliferator activated receptor gamma antagonist GW9662. No effect of either rosiglitazone or metformin was observed on proinsulin promoter activity. Metformin stimulated IPF1 nuclear accumulation and DNA binding activity in a time-dependent manner, with maximal effects observed after 2 h. CONCLUSIONS/INTERPRETATION: Metformin and rosiglitazone have direct effects on beta cell gene expression, suggesting that these agents may play a previously unrecognised role in the direct regulation of pancreatic beta cell function.

Active Transport, Cell Nucleus↗

PubMed2004

Renal tumors in young adults.

PURPOSE: The clinical and pathological features of solid or complex cystic renal masses in young adults have not been defined. We present our experience with patients 17 to 45 years old with such renal masses to define the incidence of malignant vs benign lesions, familial tendencies and clinical outcomes. MATERIALS AND METHODS: The medical records of all patients 17 to 45 years old who presented with a solid or suspicious complex cystic renal mass at 2 tertiary care hospitals between 1988 and 2002 were retrospectively reviewed. Pertinent clinical information was compiled, including age, gender, mode of presentation, renal function, year and type of surgery, pathological analysis and survival data. RESULTS: There were 114 evaluable patients who underwent a total of 119 nephrectomies. Mean patient age was 37.1 years and males comprised 56.1% of the population. Twelve patients had familial renal cell carcinoma (RCC), the von Hippel-Lindau syndrome. Mode of presentation for patients with sporadic disease was symptomatic (55.9%), incidental (35.3%) or unknown (8.8%). Radical nephrectomy, partial nephrectomy and nephroureterectomy were performed in 80 kidneys (67.2%), 37 (31.1%) and 2 (1.7%), respectively. Malignant lesions comprised 79.8% of all masses and 95.8% of these were renal cell carcinoma. Of the RCCs 75.8% were grade 1 or 2 and 89% were organ confined. Young women were much more likely than men to have a benign lesion (36.0% vs 9.5%, p <0.01) and the diversity of histologies was impressive (of the 24 total benign masses 9 were different tumor types). With an average followup of 38.3 months overall survival is 90.2%. Among patients with RCC 84.9% are alive and cancer-free, 11.6% are dead from disease and 3.5% are alive with recurrent disease. CONCLUSIONS: We report the largest known series of solid or suspicious complex renal masses in young adults. As expected, familial tumors are more common in this population. While RCC is the most common tumor, a wide variety of potential pathological outcomes are possible, particularly in women, who were much more likely to have a benign lesion. RCC in this patient population appears to have a favorable prognosis, despite symptomatic presentation in the majority of cases.

Adolescent↗

PubMed2001

Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate.

BACKGROUND: Prostate cells secrete many molecules capable of regulating angiogenesis; however, which of these actually function as essential regulators of neovascularization is not yet clear. METHODS: Functional angiogenic mediators secreted by normal and diseased prostate cells were identified using an in vitro angiogenesis assay. These factors were quantified by immunoblot or ELISA and localized in tissue by immunohistochemistry. RESULTS: Normal prostate epithelial cell secretions were anti-angiogenic due to inhibitory thrombospondin-1 (TSP-1) whereas this inhibitor was decreased in the pro-angiogenic secretions derived from benign prostatic hyperplasia (BPH) and cancer cells. This pro-angiogenic activity depended primarily on fibroblast growth factor-2 (FGF-2) and/or vascular endothelial growth factor (VEGF) whose secretion was increased. Immunolocalization studies confirmed that the changes detected in vitro also occurred in vivo. CONCLUSIONS: During disease progression in the prostate, production of TSP-1, the major inhibitor, is down-regulated while that of stimulatory FGF-2 and/or VEGF rise, leading to the induction of the new vessels necessary to support tumor growth.

Adolescent↗

PubMed2001

Biogenic production of cyanide and its application to gold recovery.

Chromobacterium violaceum is a cyanogenic (cyanide-producing) microorganism. Cyanide is used on an industrial scale to complex and recover gold from ores or concentrates of ores bearing the precious metal. A potentially useful approach in gold mining operations could be to produce cyanide biologically in relatively small quantities at the ore surface. In this study, C. violaceum grown in nutrient broth formed a biofilm and could complex and solubilize 100% of the gold on glass test slides within 4-7 days. Approximately 50% of the cyanide- recoverable gold could be mobilized from a biooxidized sulfidic-ore concentrate. Complexation of cyanide in solution by gold appeared to have a beneficial effect on cell growth--viable cell counts were nearly two orders of magnitude greater in the presence of gold-coated slides or biooxidized ore substrates than in their absence. C. violaceum was cyanogenic when grown in alternative feedstocks. When grown in a mineral salt solution supplemented with 13.3% v/v swine fecal material (SFM), cells exhibited pigmentation and suspended cell concentrations comparable to cultures grown in nutrient broth. Glycine supplements stimulated production of cyanide in 13.3% v/v SFM. In contrast, glycine was inhibitory when added at the time of inoculation in the more concentrated SFM, decreasing cell numbers and reducing ultimate bulk-solution cyanide concentrations. However, aeration and addition of glycine to stationary phase cells grown on 13.3% v/v SFM anaerobically resulted in rapid production and high concentrations (up to 38 mg l(-1)) of cyanide. This indicates that biogenesis of cyanide may be supported in remote areas using locally produced and inexpensive agricultural feedstocks in place of commercial media.

Animals↗

PubMed2001

Hand-assisted vs. retroperitoneal laparoscopic nephrectomy.

PURPOSE: We retrospectively compared our initial experience with the hand-assisted and retroperitoneal laparoscopic nephrectomy techniques to determine if there are important differences between these approaches. PATIENTS AND METHODS: Twenty-four laparoscopic cases consisting of 12 hand-assisted and 12 retroperitoneal nephrectomies were compared. All cases but one were radical nephrectomies with intact specimen extraction performed for suspected stage T1 neoplasms. Data were collected from medical records and a postoperative questionnaire. To determine if significant learning curves existed, the first six nephrectomies in each group were compared with the second six nephrectomies on the basis of operative criteria. The two groups did not differ significantly in age, body mass index, ASA rating, or number of previous abdominal operations. RESULTS: Although the mean tumor volume was greater in the hand-assisted group than the retroperitoneal group, the difference did not quite reach statistical significance (91.19 v 24.7 cc3; P = 0.06). The mean operative time, estimated blood loss, narcotic use (milligrams of intravenous morphine equivalent), hours to oral intake, hospital stay, and estimated percent activity at 2 weeks for the hand-assisted group (238.33 min, 293.75 mL, 35.7 mg, 17.56 hours, 4.4 days, 74.75%, respectively) were not significantly different from the values in the retroperitoneal group (255.83 min, 141.67 mL, 24.5 mg, 22.36 hours, 3.6 days, 76.91%). We found no significant difference in the mean operative times for the first and second six cases in either group. CONCLUSION: In the initial experience and comparison of hand-assisted and retroperitoneal laparoscopic nephrectomy, we found no significant differences in operative time, estimated blood loss, narcotic usage, hours to oral intake, hospital stay, or activity level at 2 weeks postoperatively. A randomized trial is under way at our institution.

Adult↗

PubMed2001

The role of hypoxia and p53 in the regulation of angiogenesis in bladder cancer.

PURPOSE: Our previous studies defined thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF) as the primary mediators of angiogenesis in the bladder and the loss of inhibitory TSP-1 as a key event in the transition to an angiogenic phenotype during bladder cancer development. We evaluated the role of p53, which is commonly inactivated in bladder cancer, and hypoxia in the regulation of angiogenesis in the bladder. MATERIALS AND METHODS: The p53 status was modulated in normal urothelial and bladder cancer cells, and conditioned media was collected under normal oxygen or hypoxic (0.5% O2) conditions. Angiogenic activity was evaluated with the endothelial cell migration assay, and the levels of secreted TSP-1 and VEGF were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. RESULTS: Retroviral mediated expression of the E6 oncoprotein reduced wild-type p53 levels in normal urothelial cells by greater than 90% but did not significantly alter TSP-1 or VEGF levels, while total inductive and inhibitory activities remained unchanged. Adenoviral mediated expression of wild-type p53 was confirmed in 4 bladder cancer cell lines by Western blot analysis for p53 and its downstream effector protein p21 (2.5 to 5.0-fold increase). TSP-1 levels remained unchanged but the levels of secreted VEGF in the high grade UMUC-3 and 253J cell lines were significantly decreased 5 to 50-fold and a corresponding decrease in net angiogenic activity was observed. However, (increased expression) of p53 had no effect on the angiogenic activity of the low grade RT4 or high grade HT1376 bladder cancer cells. Hypoxia converted normal urothelial cell derived conditioned media from anti-angiogenic to angiogenic and increased the angiogenic activity of bladder cancer cell derived conditioned media. This change was due to 2.5 to 6-fold hypoxic up-regulation of VEGF because the expression of inhibitory TSP-1 was not significantly altered. CONCLUSIONS: Our results suggest that p53 does not regulate angiogenesis in the bladder in the setting of an otherwise normal genome and gene therapy with wild-type p53, which is currently being studied for this cancer, may have only limited effects on angiogenesis. In contrast, hypoxia regulates angiogenesis in this system, primarily through its effects on VEGF.

Blotting, Western↗

PubMed2001

Solitary fibrous tumor of the prostate a report of 2 cases and review of the literature.

We report 2 cases of solitary fibrous tumor of the prostate. Histologically, both tumors demonstrated a multipatterned architecture with varying degrees of collagenization and hemangiopericytoma-like foci, and both were composed of CD34-immunopositive spindled cells that insinuated themselves between strips of collagen. The tumor in case 1 was well circumscribed and showed minimal mitotic activity or pleomorphism, whereas the tumor in case 2 was more cellular, less collagenous, had a more diffuse growth pattern, and exhibited cytologic atypia and high mitotic activity. Prostatic solitary fibrous tumor must be distinguished from other spindle cell tumors reported to occur in the prostate. To our knowledge, these cases represent only the fifth and sixth reported cases of prostatic solitary fibrous tumor.

Aged↗

PubMed2000

Contemporary management of renal cell carcinoma with coexistent renal artery disease: update of the Cleveland Clinic experience.

OBJECTIVES: To treat concurrent renal cell carcinoma (RCC) and renal artery disease (RAD), which pose an unusual and challenging management dilemma. METHODS: Before June 1998, 48 patients presented with localized RCC and RAD affecting all the functioning renal parenchyma. These patients were grouped into four distinct categories: group 1, a solitary kidney with RCC and RAD (n = 8); group 2, bilateral RCC and coexistent RAD (n = 9); group 3, unilateral RCC and contralateral RAD (n = 15); and group 4, unilateral RCC and bilateral RAD (n = 16). The most common cause of RAD was atherosclerosis (n = 40), followed by medial fibroplasia (n = 5), renal artery aneurysm (n = 2), and arteriovenous malformation (n = 1). RESULTS: All patients underwent complete surgical excision of RCC. A nephron-sparing operation was performed preferentially (44 patients), and bilateral renal cancer operations were staged. Eleven patients underwent surgical renal vascular reconstruction in conjunction with either partial (n = 9) or radical (n = 2) nephrectomy. In 2 patients, renal revascularization was accomplished by percutaneous transluminal angioplasty before tumor excision. No perioperative deaths occurred. Postoperatively, preservation of renal function was achieved in 47 patients; 1 patient required chronic dialysis. The overall and cancer-specific 5-year patient survival rates in this series were 66% and 90%, respectively. At a mean follow-up of 58 months, 28 patients were alive with no evidence of malignancy. Six patients died of metastatic RCC, and 14 died of unrelated causes with no evidence of malignancy. CONCLUSIONS: Nephron-sparing surgery combined with selective renal arterial reconstruction can yield gratifying results in this complex patient population.

Adult↗

PubMed2000

Glucose regulates islet amyloid polypeptide gene transcription in a PDX1- and calcium-dependent manner.

Islet amyloid polypeptide (IAPP) and insulin are expressed in the beta-cells of the islets of Langerhans. They are co-secreted in response to changes in glucose concentration, and their mRNA levels are also regulated by glucose. The promoters of both genes share similar cis-acting sequence elements, and both bind the homeodomain transcription factor PDX1, which plays an important role in the regulation of the insulin promoter and insulin mRNA levels by glucose. Here we examine the role of PDX1 in the regulation of the human IAPP promoter by glucose. The experiments were facilitated by the availability of a human beta-cell line (NES2Y) that lacks PDX1. NES2Y cells also lack operational K(ATP) channels, resulting in a loss of control of calcium signaling. We have previously used these cells to show that glucose regulation of the insulin gene is dependent on PDX1, but not calcium. In the mouse beta-cell line Min6, glucose (16 mm) stimulated a 3.5-4-fold increase in the activity of a -222 to +450 IAPP promoter construct compared with values observed in 0.5 mm glucose. In NES2Y cells, glucose failed to stimulate transcriptional activation of the IAPP promoter. Overexpression of PDX1 in NES2Y cells failed to reinstate glucose-responsive control of the IAPP promoter. Glucose effects on the IAPP promoter were observed only in the presence of PDX1 when normal calcium signaling was restored by overexpression of the two K(ATP) channel subunits SUR1 and Kir6.2. The importance of calcium was further emphasized by an experiment in which glucose-stimulated IAPP promoter activity was inhibited by the calcium channel blocker verapamil (50 microm). Verapamil was further shown to inhibit the stimulatory effect of glucose on IAPP mRNA levels. These results demonstrate that like the insulin promoter, glucose regulation of the IAPP promoter is dependent on the activity of PDX1, but unlike the insulin promoter, it additionally requires the activity of another, as yet uncharacterized factor(s), the activity of which is calcium-dependent.

Amyloid↗

PubMed2000

Clinical aspects of inhaled anticholinergic therapy.

Anticholinergic therapy is directed toward muscarinic receptors within the lung. Inhaled quaternary muscarinic antagonists are used because they cause less systemic adverse effects than other types of antimuscarinic drugs. Of the 5 possible muscarinic receptors, the lung contains three: M1, M2, and M3. Antagonism of the M1 and M3 receptors results in bronchodilation, primarily in the larger airways. The efficacy of the antimuscarinic bronchodilators cannot be entirely explained by this mechanism, and there is probably peripheral activity as well. The use of inhaled antimuscarinic drugs is well tolerated, and the efficacy is maintained with chronic use. Although ipratropium is the first-line therapy for symptomatic COPD, it and other similar drugs can also be used to treat other obstructive diseases. Ipratropium is available in an MDI, in solution for small-volume nebulizer, and in combination with albuterol in an MDI. Newer antimuscarinic agents are being developed that are more selective for the M1 and M3 sites and last longer. Research is continuing to better understand the sites of action of these agents as well as to develop even more effective drugs.

Administration, Inhalation↗

PubMed1999

Inhibitory effect of pax4 on the human insulin and islet amyloid polypeptide (IAPP) promoters.

Pax4 is a paired-box transcription factor that plays an important role in the development of pancreatic beta-cells. Two Pax4 cDNAs were isolated from a rat insulinoma library. One contained the full-length sequence of Pax4. The other, termed Pax4c, was identical to Pax4 but lacked the sequences encoding 117 amino acids at the COOH-terminus. Pax4 was found to inhibit the human insulin promoter through a sequence element, the C2 box, located at -253 to -244, and the islet amyloid polypeptide promoter through a sequence element located downstream of -138. The inhibitory activity of Pax4 was mapped to separate regions of the protein between amino acids 2-230 and 231-349.

Amyloid↗

PubMed1998

Molecular mediators of angiogenesis in bladder cancer.

Bladder tumors are characterized by markedly increased angiogenesis when compared to the normal urothelium (NU) from which they are derived. Here, we use both cultured cells and immunohistochemistry to demonstrate a primary regulatory role for thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in the development of bladder tumor angiogenesis. Secretions from bladder cancer (CA) cells stimulated endothelial cell migration and corneal neovascularization, whereas those from NU cells were inhibitory. The antiangiogenic activity of NU cells was primarily due to secreted TSP-1 because neutralizing antibodies completely relieved the inhibition. Neutralizing antibodies to several putative angiogenesis inducers identified vascular endothelial growth factor (VEGF) and, to a lesser extent, basic fibroblast growth factor as the primary inducers secreted by bladder cancer cells. The secretion of TSP-1 by low- and high-grade cancer cells was reduced >94% when compared to NU cells, and this loss of inhibitory TSP-1 accounted for the development of an angiogenic phenotype because both NU cells and cancer cells secreted similar levels of total stimulatory activity and VEGF. Immunohistochemistry showed that TSP-1 was significantly reduced in all grades of bladder cancer when compared to NU, whereas VEGF staining remained relatively constant. Taken together, these data suggest that down-regulation of TSP-1 secretion is a key event in the switch from an antiangiogenic to an angiogenic phenotype, which occurs early in the development of bladder cancer.

Cells, Cultured↗

PubMed1998

Renal cryosurgery: experimental evaluation of treatment parameters.

OBJECTIVES: Cryosurgery represents a minimally invasive alternative for the management of small or equivocal lesions of the kidney. We evaluated the relationship between ultrasonographic appearance and intrarenal temperatures and the effect of renal artery occlusion on the efficacy of the freezing process in a canine model. METHODS: Ten animals were treated with intraparenchymal cryoablative therapy with (n = 5) or without (n = 5) renal artery occlusion using a rapid freeze technique. Intrarenal temperatures were measured 1.0 cm away from the cryoprobe at various times during the freezing process. The distance from the cryoprobe to the ice ball as monitored by ultrasonography was also determined. The contralateral kidney was removed to facilitate studies of renal function and all animals were killed on day 28 for autopsy and histopathologic examination. RESULTS: A target temperature of less than -20 degrees C was achieved 3.1 mm behind the ice ball in all animals tested. The ice ball stabilized at a radius of 16 mm with prolonged treatment, suggesting that multiple probes will be required to treat renal lesions greater than 2.5 cm in diameter. Renal artery occlusion did not significantly alter the freezing process and provided no practical advantage. Renal function remained stable (final serum creatinine level 1.5 mg/dL or less) in all but 1 animal in which an obstructive stricture of the ureteropelvic junction developed. Effective tissue ablation was confirmed at the treatment site in all instances. CONCLUSIONS: Renal cryoablative therapy is a nephron-sparing modality that can be delivered in a safe, efficacious, and reproducible manner. The treatment parameters defined in this study should allow for intelligent patient selection and rational administration of renal cryotherapy.

Animals↗

PubMed1997

Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma.

Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INF gamma, TNF alpha, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNF alpha, IFN gamma, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.

Carcinoma, Renal Cell↗

PubMed1997

Advances in angiogenesis research: relevance to urological oncology.

PURPOSE: Important advances in angiogenesis research are reviewed along with recent data implicating angiogenesis in the pathogenesis of urological malignancies. MATERIALS AND METHODS: The current understanding of angiogenesis and its importance in tumor biology is summarized. The rationale for anti-angiogenic therapy is reviewed and the clinical experience with these agents is discussed. An extensive literature search of angiogenesis in urological malignancies was performed. RESULTS: Quantitative immunohistochemistry for endothelial antigens suggests that, as is the case with many other tumors, induction of angiogenesis contributes to the malignant phenotype of prostate and bladder carcinomas. Anti-angiogenic agents have demonstrated efficacy against urological tumors in experimental systems, and recent data suggest that these agents may also be useful for chemoprophylactic purposes. Putative angiogenesis inducers specific for each of the major urological malignancies have been identified. Quantitation of the expression of angiogenesis inducers and estimation of microvessel density have demonstrated prognostic value for urological malignancies. CONCLUSIONS: The available data indicate that angiogenesis has an important role in the progression and metastasis of urological malignancies. Preclinical data coupled with experience in other cancers indicate that combining anti-angiogenic therapy with conventional treatment modalities has the potential to improve dramatically our management of these malignancies. Further research will be needed to define the mechanisms controlling angiogenesis in urological malignancies and to determine if any of the angiogenic correlates will be of genuine clinical use. The rapid pace of research in this field suggests that this aspect of tumor biology will soon have an increasingly important role in the evaluation and treatment of urological cancers.

Angiogenesis Inducing Agents↗

PubMed1997

Prospective evaluation of fine needle aspiration of small, solid renal masses: accuracy and morbidity.

OBJECTIVES: To determine the accuracy and clinical utility of fine needle aspiration (FNA) of small, solid renal masses. METHODS: A total of 25 patients with small (less than 5.0 cm), solid, clinically localized renal masses were prospectively identified and evaluated with computed tomography guided FNA with analysis for presence of malignant cells and determination of nuclear grade. The final pathologic findings were used for comparison in each case. All patients had renal cell carcinoma and were managed with radical or partial nephrectomy; 3 had low-grade lesions (Fuhrman's grade 1/4), 2 had high-grade lesions (Fuhrman's grade 4/4), and all other patients had intermediate-grade lesions (Fuhrman's grade 2/4 or 3/4) on final histopathologic assessment. RESULTS: Overall, 10 aspirations yielded diagnostic malignant cells, and 9 were read as rare as rare atypical cells suspicious for malignancy. The remainder were negative (n = 6). Correlation with final nuclear grade was observed in eight instances and discordance in two instances. Subcapsular hematomas were observed at the time of surgery in 10 patients, but in no instance was the operation adversely affected. CONCLUSIONS: The diagnostic yield of FNA of small, solid renal masses appears to be too low to justify the potential morbidity of the procedure.

Biopsy, Needle↗