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Biomedical subjects

M Susani

Publications and source records attributed to M Susani.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of the VEGF-receptor Flt-1 in benign, premalignant and malignant prostate tissues.

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most potent regulators of angiogenesis and has been shown to act upon two tyrosine kinase family receptors: c-fms-like tyrosine kinase (Flt-1) and fetal liver kinase. Preliminary reports have emphasized that expression of VEGF receptors is endothelial cell-specific. In this study we verified the localization and distribution of Flt-1 protein and mRNA expression in prostatic adenocarcinoma (CaP) as well as prostate intraepithelial neoplasia (PIN) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: 30 selected surgical specimens exhibiting areas with CaP, PIN and BPH histology were evaluated for Flt-1 protein expression by immunohistochemistry. Results were compared with tumor differentiation (Gleason-Score), serum-PSA and clinical followup. Flt-1 synthesis by prostatic carcinoma cell lines, freshly isolated BPH epithelial cells (BPH-EC) and stromal cells was investigated using RT-PCR and intron spanning primer. RESULTS: VEGF receptor Flt-1 specific anti-sera revealed significant staining of prostatic endothelial cells, but the reactivity was not restricted to endothelial cells. BPH-epithelial cells of all specimens reacted significantly with anti-Flt-1. In contrast, tumor cells failed to react with anti-Flt-1 in 56% of the specimens. BPH-EC revealed a uniform anti-Flt-1 reactivity, which was less pronounced and weaker in PIN. Loss of anti-Flt-1 reactivity of prostatic tumor cells did not correlate with preoperative PSA serum levels but increased with tumor dedifferentiation. Interestingly, tumor cells of all CaP specimens with a Gleason score of >8 exhibit no anti-Flt-1 immunoreactivity. Accordingly while PC3, DU145 and LNCaP cells were negative when tested using RT-PCR all BPH tissue derived BPH-EC revealed Flt-1 coding mRNA expression. CONCLUSIONS: Widespread distribution of VEGF receptor Flt-1 in BPH, PIN and prostate cancer specimens suggests that VEGF function in prostate is not restricted to endothelial cells and angiogenesis. However, since the receptor is lost in CaP cells and with tumor dedifferentiation, these yet unknown effects of VEGF on epithelial cells are obviously suppressed with malignant transformation.

Adenocarcinoma↗
PubMed1999

Quick-staining urinary cytology and bladder wash image analysis with an integrated risk classification: a worthwhile improvement in the follow-up of bladder cancer?

BACKGROUND: With an end toward an increase in patient quality of life, morphologic methods were tested for their combinatory value in expanding the effectiveness of follow-up appointments and finding a more specific supervision of patients with bladder cancer. METHODS: Voided urine and bladder washing specimens were gathered in 223 follow-up sessions of 124 patients with a history of bladder cancer. Hemacolor (Merck, Darmstadt, Germany)-stained cytospin preparations of voided urine specimens were ready for diagnosis within 15 minutes, and results were available shortly before cystoscopy. Feulgen-Schiff-stained cytospin preparations of bladder washings entered the image analysis system. A special software was used to classify the DNA histogram by a risk factor for bladder cancer. RESULTS: Follow-up of patients revealed 83 tumor recurrences. Depending on the grade of the underlying tumor, the sensitivity of quick-staining cytology was 86.4%, 46.2%, or 13.6% for grade 3 to grade 1 TCC, respectively. Cytology and image analysis data demonstrated complementary potency. The combination of methods increased sensitivity to 90.9%, 66.7%, and 31.8%, respectively. Although 24 of 140 image analyses denoted high risk for bladder cancer without simultaneously visible tumor, correct evidence of high risk could be found for 92.2%. CONCLUSIONS: The combinatory use of quick-staining urinary cytology and bladder wash image analysis was demonstrated to be most valuable in diagnosing recurrent bladder cancer and selecting patients needing more intensive follow-up. At a minimum of patients discomfort, the tested combination also seems helpful to surpass diagnostic limits in cystoscopy and cytology caused by therapeutic effects on the bladder epithelium. Cancer (Cancer Cytopathol)

Adolescent↗
PubMed1999

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers.

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.

Adult↗
PubMed1999

Tyrosine kinases expressed in vivo by human prostate cancer bone marrow metastases and loss of the type 1 insulin-like growth factor receptor.

An important biological feature of prostate cancer (PCa) is its marked preference for bone marrow as a metastatic site. To identify factors that may support the growth of PCa in bone marrow, expression of receptor and nonreceptor tyrosine kinases by androgen-independent PCa bone marrow metastases was assessed. Bone marrow biopsies largely replaced by PCa were analyzed using reverse transcriptase-polymerase chain reaction amplification with degenerate primers that amplified the conserved kinase domain. Sequence analyses of the cloned products demonstrated expression of multiple kinases. Expression of the receptor and nonreceptor tyrosine kinases, alpha platelet-derived growth factor receptor and Jak 1, respectively, was confirmed by immunohistochemistry. In contrast, the type 1 insulin-like growth factor receptor, thought to play a role in PCa development, was lost in metastatic PCa. These results implicate several specific growth factors and signaling pathways in metastatic androgen-independent PCa and indicate that loss of the type 1 insulin-like growth factor receptor contributes to PCa progression.

Bone Marrow Neoplasms↗
PubMed1999

Predictability and significance of multifocal prostate cancer in the radical prostatectomy specimen.

Multifocal prostate cancer has been reported in 50-76% of all cases of radical retropubic prostatectomy (RRP) specimens, but the clinical and prognostic significance of this finding is still unclear. A retrospective analysis of patients who underwent RRP between 1993 and 1997 was performed. Preoperative screening parameters and 4-mm RRP specimen sections were examined. The location, Gleason score, and extracapsular extension of the tumor recorded. Three hundred eight cases were reviewed. Mean follow-up was 4.2 +/- 1 years (range 2-6 years). Two hundred six patients (66.9%) had multifocal prostate cancer and 102 (33.1%) had unifocal prostate cancer. Of those with multifocal disease, 63% had two foci and 37% had three or more foci. There were statistical significant differences between both groups with respect to preoperative prostate-specific antigen (PSA) density of the transition zone (PSA-TZ), free/total (f/t) PSA, as well as percentage of patients with organ confined disease, high-grade tumors, and local recurrence. PSA-TZ (p = .001) and f/t PSA (p = .004) were significantly different between patients with unifocal and multifocal disease (0.9 vs. 2.2 ng/mL/cc and 18% vs. 6.5%, respectively). However, preoperative PSA (11.2 vs. 12.8 ng/mL; p = .09) and PSA density (0.17 vs. 0.19 ng/mL/cc; p = .07) were not able to predict unifocality or multifocality. These data suggest that multifocal prostate cancer is associated with higher grade, stage, and recurrence rate than unifocal prostate cancer. Preoperative PSA-TZ (> 1.5 ng/mL/cc) and f/t PSA (<9%) may predict multifocality in the RRP specimen.

Aged↗
PubMed1998

High incidence of nephrogenic adenoma of the bladder after renal transplantation.

BACKGROUND: Tumors of the bladder termed nephrogenic adenomas in kidney allograft recipients are believed to develop as urothelial metaplastic proliferations in response to mechanical trauma, chemical noxae, irradiation, and bacterial or viral pathogens. We report on the incidence of nephrogenic adenoma of the bladder in patients who received renal transplants during a period of 7 years and 3 months at the University Hospital of Vienna. METHODS: Diagnosis was obtained by cystoscopy and histological analysis. Nephrogenic adenoma was treated by transurethral electroresection and administration of antibiotics in case of urinary tract infections. Follow-up consisted of cytological controls of urine and bladder irrigation fluid as well as of cystoscopy every 3 months. RESULTS: In 7 of 1328 renal allograft recipients, nephrogenic adenoma could be detected after 7 to 60 months following renal transplantation. In five patients, recurrence was detected 9 to 23 months after diagnosis of the initial lesion. No evidence of malignant degeneration was observed in any patient. Nephrogenic adenoma was not related to immunosuppressive therapy, cytomegalovirus disease, or gancyclovir therapy. CONCLUSIONS: We suggest that after successful transurethral electroresection of nephrogenic adenomas, cytological controls are adequate every 3 months. Only in renal transplant patients with recurrence of voiding disturbances, macrohematuria, or urinary tract infection are cystoscopy and biopsy indicated in the routine follow-up regimen.

Adenoma↗
PubMed1998

N-acetylneuraminic acids (nana): a potential key in renal calculogenesis.

N-Acetylneuraminic acids (NANA) promote binding of calcium ions to macromolecules and cells, increase the intrinsic viscosity of glycoproteins and facilitate gel formation in water. Since these properties are crucial in urinary calculogenesis, we evaluated NANA levels in urine and serum as well as their expression in kidney tissues. Using a modified thiobarbituric acid assay, the evaluation of free and bound NANA in 24-h urine samples revealed a ratio of 1.87 in 33 non-stone-formers but a reversed ratio of 0.84 in 41 recurrent calcium oxalate stone-formers. Time kinetics revealed a gradual rise in NANA expression until 48 h of culture and a significantly higher release into supernatants of papillary renal epithelial cells (REC) when compared with cortical REC. To examine NANA distribution in kidney tissues, paraffin-embedded biopsies from five normal and six stone-forming kidneys were labeled with the biotinylated NANA-specific lectins Maackia amurensis (MAA) and Sambucus nigra (SNA). Immunohistochemistry revealed intense luminal MAA reactivity of distal tubular REC and collecting ducts in 96.7% and 91.5% of normal and stone-forming kidneys respectively. By contrast, there was a marked difference between normal and stone-forming kidneys for SNA reactivity (17.7% vs 95%) at the same locations. Finally, the glycocalyx of recurrent stone-formers showed altered sialylglycoside linkages [alpha(2,6) instead of alpha(2,3)] that may indicate an altered REC function. Given the calcium-binding potential of NANA, their increased local concentration within the glycocalyx layer in the distal nephron may either initiate stone formation or facilitate attachment of microcrystals to REC.

Adult↗
PubMed1998

Expression of bcl-2, bcl-x, bax and bak in renal parenchyma, oncocytomas and renal cell carcinomas.

Proteins of the bcl-2 family are important regulators of programmed cell death. Alterations in the expression of these proteins may contribute to the progression of cancer. Expression of bcl-2, bcl-x, bax and bak was investigated by immunohistochemistry and Western-blotting of regular and alterated renal parenchyma as well as in 57 renal cell carcinomas. Bcl-2, bcl-x and in part bax were found to be overexpressed in inflammed renal parenchyma, whereas atrophic tubuli predominantly stained for bcl-2 and to a lesser degree for bcl-x and bax. Only little bak expression was detected in alterated tubuli. Moderate to strong expression for bcl-2, bcl-x, bax and bak was found in 24, 38, 2 and 13 of 57 carcinomas, respectively. Bcl-2, bcl-x, bax and bak expression were correlated to tumor type. Chromophilic carcinomas stained stronger for bcl-2, bcl-x and bax, whereas chromophobic carcinomas stained stronger for bcl-x, bax and bak compared to clear cell carcinomas. Expression of bak correlated with that of bcl-x and with an unfavorable histology as indicated by nuclear grading in these tumors. Our findings suggest that expression of bcl-2 and bcl-x may be important for cell survival only in a subset of renal cell carcinomas, and that the anti-apoptotic effect of these proteins appears to be frequently bypassed possibly by other factors impeding programmed cell death.

Adenoma, Oxyphilic↗
PubMed1998

Prostate specific antigen density of the transition zone for predicting pathological stage of localized prostate cancer in patients with serum prostate specific antigen less than 10 ng./ml.

PURPOSE: Prostate specific antigen (PSA) density of the transition zone, which is the density of serum PSA related to the volume of the transition zone, has been recently demonstrated to enhance prostate cancer prediction in patients with intermediate PSA levels. We further investigated the usefulness of PSA-transition zone for predicting extraprostatic extension in clinically localized prostate cancer. MATERIALS AND METHODS: Measuring the transition zone of the prostate by ultrasound using the prolate ellipsoid method, PSA-transition zone values were calculated prospectively in 198 patients with clinically localized prostate cancers and serum PSA less than 10.0 ng./ml. who underwent radical retropubic prostatectomy. The ability of PSA-transition zone to predict extracapsular disease in the surgical specimen was compared to Gleason score, serum PSA, PSA density of the total prostate and percent free PSA using univariate or multivariate analysis as well as receiver operating characteristics curves. RESULTS: A total of 104 patients (52.5%) had pathologically organ confined prostate cancer while 94 of 198 (47.5) had extracapsular disease. PSA-transition zone levels were significantly higher in extracapsular disease than organ confined cancers (0.84 versus 0.42 ng./ml./cc, p <0.00001). Using multivariate analyses PSA-transition zone and Gleason score were the most significant predictors of extracapsular disease. The area under the curve was larger for PSA-transition zone (0.825) than any other parameter (p <0.004 versus PSA density and p <0.001 versus PSA, percent free PSA or Gleason score). A cutoff of 1.00 ng./ml./cc for PSA-transition zone provided 95.1% specificity and 28.8% sensitivity for predicting extracapsular disease. Probability plots using the best combination of independent variables for predicting extraprostatic extension were developed. CONCLUSIONS: These data demonstrate that the use of the PSA-transition zone may be of additional value for indicating which patients with clinically localized prostate cancer and PSA less than 10.0 ng./ml. are at high risk for extracapsular disease.

Aged↗
PubMed1998

Transcutaneous high-intensity focused ultrasound and irradiation: an organ-preserving treatment of cancer in a solitary testis.

OBJECTIVES: The aim of this study was to determine the feasibility and safety of transcutaneous ablation of human testicular tissue by high-intensity focused ultrasound (HIFU). METHODS: Transcutaneous ablation of human testicular tissue by HIFU was performed with equipment previously developed for transrectal prostate ablation. This device utilizes a piezoceramic transducer operating at 4.0 MHz with a site-intensity of 1,600-2,000 W/cm2. To study the histological impact of transcutaneous HIFU, tests of 4 patients with prostate cancer were subjected to transcutaneous HIFU-therapy prior to scrotal orchiectomy in a phase I trial. In a phase II clinical trial, 4 patients with the typical sonographic pattern of a tumor in a solitary testis were treated with transcutaneous HIFU as a minimally invasive organ-preserving approach followed by a 6 weeks' course of prophylactic irradiation of the testis with 20 Gy. In all 4 patients, the contralateral testis had been previously removed for testis cancer. RESULTS: Histologically, HIFU-treated areas exhibited signs of cellular necrosis in all cases (n = 4). The border between viable and necrotic tissue was extremely sharp comprising only 5-7 cell layers. In the phase II clinical study, we aimed to ablate the entire cancer in a single therapeutic HIFU session. HIFU treatment was performed under general anesthesia. As negative side effects we observed a cutaneous thermolesion in 1 individual. One patient refused to undergo postoperative irradiation and developed a local failure. This patient underwent radical orchiectomy. Another patient received two cycles of chemotherapy for a single suspicious retroperitoneal lymph node diagnosed 6 months after HIFU therapy. Three patients are tumor-free with a follow-up of 16, 23 and 31 months, respectively. CONCLUSIONS: This study demonstrates the feasibility and safety of transcutaneous testicular tissue ablation by HIFU. Despite the major drawback of this technique, i.e. that no tumor histology is obtained, we believe that transcutaneous HIFU followed by irradiation has the potential to be established as a minimally invasive treatment alternative to organ-preserving surgery for tumors in a solitary testis.

Adult↗
PubMed1998

Transperineal radiofrequency interstitial tumor ablation (RITA) of the prostate.

The purpose of this study was to investigate the safety and feasibility of radiofrequency interstitial tumor ablation (RITA) in localized prostate cancer (PCa) and to assess the predictability of the lesions obtained. In 10 patients with localized PCa (mean age 70.4 years), a total of 21 marker lesions were induced under general (n = 3), spinal (n = 4), or local anesthesia only (n = 3). Radiofrequency energy was delivered transperineally under transrectal ultrasound (TRUS) guidance. Radical prostatectomy was performed in all patients 1-7 days after RITA. The findings of intraoperative TRUS and histologic examination of the specimen were correlated. Lesions 2 x 2 x 2 cm were targeted. Postoperatively, patients were catheterized for an average of 1.8 days (range 1-3). Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm (average volume 5.86 +/- 1.63 cm3). Lesions were well defined and did not extend beyond the prostatic capsule. No complications (e.g., rectal wall injury) were noted. RITA-induced lesions were safe, feasible, technically simple, and resulted in lesions well predictable in size and location. On histologic examination, well-defined areas of coagulative necrosis were documented. No damage to the periprostatic tissue was noted. The procedure can be performed with spinal or local anesthesia only.

Aged↗
PubMed1997

Pathogenic antibodies inhibit the binding of apolipoproteins to megalin/gp330 in passive Heymann nephritis.

Megalin/gp330 is an endocytic receptor that internalizes multiple ligands including apolipoproteins E (apo E) and B100 (apo B). Megalin is the main antigenic target in passive Heymann nephritis (pHN), where it binds circulating autoantibodies leading to the formation of subepithelial immune deposits (ID)-the hallmark of pHN. Apo E and apo B were found recently to accumulate within these IDs, and evidence was provided that their lipids may undergo peroxidation, causing glomerular basement membrane damage and proteinuria. Here we investigated if ID-forming antimegalin IgG can inhibit the binding and internalization of apo E-betaVLDL (very low density lipoprotein) by megalin, and lead to their accumulation within IDs. By immunoelectron microscopy, apo E and apo B were detected in clathrin-coated pits and multivesicular bodies of podocytes in control rats, suggesting that the uptake of lipoproteins is a constitutive function of the glomerular epithelium. When pHN was induced by intravenous injection of antimegalin IgG, apo E and apo B were found within IDs by immunofluorescence and immunoelectron microscopy. Bound antibodies eluted from glomeruli of rats with pHN were found to inhibit the binding and internalization of apo E-enriched betaVLDL by megalin. These results indicate that pHN-inducing antimegalin IgG is capable of interfering with the uptake of lipoproteins by megalin in vivo during the formation of IDs.

Animals↗
PubMed1997

Soft-tissue effects of the holmium:YAG laser: an ultrastructural study on oral mucosa.

BACKGROUND AND OBJECTIVE: The specifics of the ablation mechanism of the holmium:YAG laser remain largely unexplored. Following laser exposure to the oral mucosa of rats, the ultrastructural damage profile obtaining to varying degrees in blood vessels, erythrocytes, nerves, and muscle cells was examined. An attempt was made to relate the cytoplasmatic alterations to the tissue ablation modes of midinfrared lasers described in the literature. STUDY DESIGN/MATERIALS AND METHODS: The biological effects of a new pulsed holmium:YAG laser (lambda = 2,120 nm) on the oral mucosa of rats were examined by light and transmission electron microscopy. Laser incisions reaching into the muscle layer were made on different sites of the tongue of white rats. Laser energy (400 mJ, 2.5 microseconds pulse, 2 Hz) was delivered to the target via 400 microns nylon fibers. RESULTS: The fine-structural morphology of the sublingual mucosa after laser surgery of the epithelial surface revealed no carbonization layer but a 150-micron-wide zone of lacunar structures extending to the lamina propria. In the muscle cells there is partial decomposition of the cell contents resulting in the development of electron optically empty spaces within the cortical cytoplasm underneath the intact plasma membrane of the muscle cell. The organelles within the cell remain ultrastructurally intact. CONCLUSION: These features support the assumption of an additional nonthermal holmium:YAG laser-tissue interaction.

Animals↗
PubMed1997

High-level expression and purification of the major birch pollen allergen, Bet v 1.

Bet v 1, the single major allergen from birch pollen, shares IgE epitopes with all major tree pollen allergens from closely related species such as alder, hazel, hornbeam, beech, and European chestnut. Because of high sequence homologies among these allergens and the well-studied cross-reactivities on B cell epitopes, Bet v 1 is a representative model protein which can be used for in vitro studies. The cDNA coding for Bet v 1, the single major allergen from birch pollen, was cloned into the T7-based Escherichia coli expression system pMW 175/BL21(DE3) and synthesized as a nonfusion protein. In contrast to other E. coli systems (e.g., pKK233-2/JM105), this system produces high levels of readily extractable proteins corresponding to 5-10% of E. coli total protein, the percentage varying with culture conditions. The overall yield was 8-10 mg of purified recombinant protein per liter of culture medium. The recombinant allergen was purified by several steps, including ion-exchange and hydrophobic interaction chromatography. The purified recombinant allergen showed identical immunological properties with the respective natural counterpart. The use of recombinant allergens of high purity is expected to result in more accurate diagnostic procedures, but possibly also in a superior immunotherapy of Type I allergic diseases when compared with methods using crude allergen extracts containing various amounts of allergen concentrations.

Allergens↗
PubMed1997

Late ureteral obstruction after kidney transplantation. Fibrotic answer to previous rejection?

Today, the incidence of urological complications following renal transplantation is 2%-10%. Most of these complications occur within the 1st year and affect the distal ureter. We report on two patients who developed very late ureteral obstruction, 14 and 18 years after transplantation. Both patients had rejection episodes 1 and 10 months prior to the ureteral stenosis. Histological examination of one resected ureter revealed findings strongly suggestive of a rejection process. Open surgery with antirefluxive reimplantation into the bladder was successful in both patients, with a postoperative observation time of 20 and 8 months, respectively. We conclude that a percutaneous nephrostomy may be required in patients with rising creatinine and incipient hydronephrosis even long after transplantation has been performed.

Adult↗
PubMed1997

Ophthalmoplegia as an unusual initial symptom of non-Hodgkins' lymphoma in the head and neck.

Non-Hodgkins' lymphomas are relatively common tumors in the head and neck and should always be considered in the differential diagnosis of any mass lesion in this region, especially in cases with single enlarged lymphnodes of unknown origin and symptoms that can only be explained by metastasis. The diagnosis is usually established by multidisciplinary collaboration. We report our experience in managing a 48-year-old man who was found to have a non-Hodgkins' lymphoma in his neck that was complicated by a metastasis to his brain causing incomplete ophthalmoplegia, a rare primary complication. The differential diagnosis and the examinations leading to the diagnosis are discussed.

Brain Neoplasms↗