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T C Gasser

Publications and source records attributed to T C Gasser.

At least 19 recordsLinked to original sources
PubMed2006

KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer.

Molecular mechanisms of prostate cancer progression are poorly understood. Here, we studied gene amplification of the large conductance calcium-activated potassium channel alpha subunit (KCNMA1), which is located at the chromosomal region 10q22. Fluorescence in situ hybridization (FISH) revealed KCNMA1 amplification in 16% of 119 late-stage human prostate cancers and in the hormone-insensitive prostate cancer cell line PC-3. In contrast, KCNMA1 amplification was absent in 33 benign controls, 32 precursor lesions and in 105 clinically organ-confined prostate cancers. Amplification was associated with mRNA and protein overexpression as well as increased density of BK channel protein and beta-estradiol-insensitive BK currents in PC-3 cells as compared to non-amplified control cell lines. Specific blockade of BK channels by iberiotoxin or RNA(i) significantly inhibited K(+) currents and growth of PC-3 cells. The data demonstrate that 10q22 amplification drives KCNMA1 expression and cell proliferation. Thus, KCNMA1 qualifies as a promising diagnostic and therapeutic target in patients with prostate cancer.

Cell Line, Tumor↗
PubMed2006

Stress-driven collagen fiber remodeling in arterial walls.

A stress-driven model for the relation between the collagen morphology and the loading conditions in arterial walls is proposed. We assume that the two families of collagen fibers in arterial walls are aligned along preferred directions, located between the directions of the two maximal principal stresses. For the determination of these directions an iterative finite element based procedure is developed. As an example the remodeling of a section of a human common carotid artery is simulated. We find that the predicted fiber morphology correlates well with experimental observations. Interesting outcomes of the model including local shear minimization and the possibility of axial compressions due to high blood pressure are revealed and discussed.

Anisotropy↗
PubMed2006

Retroperitoneoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO): solving the technical difficulties.

OBJECTIVES: To evaluate our current practice in retroperitoneoscopic pyeloplasty in patients with ureteropelvic junction obstruction (UPJO). Special interest was paid to technical difficulties associated with the retroperitoneoscopic approach. METHODS: Our retroperitoneoscopic approach for pyeloplasty is explained step for step including the most technically challenging part: the ureteropelvic anastomosis. RESULTS: Within 49 months a total of 47 retroperitoneoscopic pyeloplasties we performed at our institution. Before pyeloplasty an endopyelotomy had failed in five patients (11%). We did not necessarily perform a ventral transposition of the anastomosis in cases with a crossing vessel. Two (4%) conversions to open surgery were required because of scarring after previous endopyelotomy and massive obesity resulting in a limited working space. There were no intraoperative complications. A recurrence of UPJO was observed in 2% (n = 1). CONCLUSION: Functional results after retroperitoneoscopic pyeloplasty are excellent and comparable to those of open surgery. However, special knowledge of retroperitoneoscopy is necessary to provide the patient with a safe and effective minimally invasive alternative to open pyeloplasty.

Adolescent↗
PubMed2005

Retroperitoneoscopic living donor nephrectomy: a comparison with the open approach in respect of early postoperative pain management.

INTRODUCTION: We retrospectively compared perioperative donor outcomes and early postoperative pain control after retroperitoneoscopic (RLDN) and standard open (OLDN) living donor nephrectomy. METHODS: One hundred donors included fifty after RLDN (37 women/13 men) and 50 after OLDN (35 women/15 men) were retrospectively analyzed for basic analgesics, for opioid consumption, and for visual analog scale (VAS) to verify the experienced pain. The donors were questioned in the morning and evening of the first through fifth postoperative days. RESULTS: The mean age of both groups was equal. The mean operating time was 149.7 +/- 48.2 minutes (60 to 270) for RLDN and 164.1 +/- 30.3 minutes (60 to 240) for OLDN (P = NS). The mean warm ischemia time was 120 +/- 36 seconds (50 to 240) and 114 +/- 31 seconds (60 to 190) for the RLDN and OLDN groups, respectively (P = NS). The mean evening VAS for RLDN versus OLDN on postoperative days 1 to 5 was: 2.1 versus 2.2 (P = NS), 0.9 versus 1.8 (P = .009), 0.5 versus 1.3 (P = .016), 0.1 versus 0.7 (P = .013), and 0.1 versus 0.7 (P = .013), respectively. In both groups there was a tendency toward a higher VAS score in the morning than in the evening. RLDN donors showed significantly earlier period free of pain (VAS = 0) than those after OLDN. There was a significant difference of being free from any opiate between both groups after surgery. CONCLUSIONS: After RLDN donors experienced less postoperative pain than after OLDN over the early postoperative days. Therefore, postoperative regional anesthesia is not necessary for donors operated by a retroperitoneoscopic approach.

Adult↗
PubMed2005

Curative surgery for solitary adrenal metastasis of pT1 G3 transitional cell carcinoma of the bladder.

A preoperative computed tomography scan in a patient undergoing radical cystectomy for pT1N0 grade 3 transitional cell carcinoma revealed a tumor in the adrenal gland. Biopsy was negative, but 2 years later computed tomography showed progression, and adrenalectomy was performed, revealing transitional cell carcinoma. Four years after cystectomy, the patient had no evidence of other metastases. We discuss surgery for solitary metastasis of transitional cell carcinoma as a curative treatment option.

Adrenal Gland Neoplasms↗
PubMed2005

Primitive neuroectodermal tumor of the kidney with hyaline cells.

Primitive neuroectodermal tumor (PNET) of the kidney is a rare disease with high malignant potential. It affects young adults and has the tendency towards early metastasis. Relying on recently available immunohistochemistry and cytogenetic investigations, today most authors define PNET as part of the same nosologic entity as Ewing's sarcoma. We present the case of a 22-year-old man with a PNET arising from the kidney with, to our knowledge, a previously undescribed finding of hyaline cells within the tumor.

Adult↗
PubMed2004

First case of lymphangioma of the bladder in an adult.

Lymphangioma is a congenital malformation consisting of a developmental or primary defect of the lymphatic channels. We report the first case of lymphangioma of the bladder in an adult and review the literature. In our case a 49-year-old man presented with irritative voiding symptoms, cystoscopy showed a non-papillary tumor between the two orifices within the trigone, and transurethral resection was performed. Three months after operation the irritative voiding symptoms had improved and cystoscopy showed no residual tumor.

Humans↗
PubMed2004

[Multiprobe FISH for enhanced prediction of recurrent bladder cancer].

The early detection of recurrent urothelial cancer is a great challenge for both urologists and pathologists. Cytology is a sensitive and highly specific tool for the diagnosis of high-grade bladder cancer and carcinoma in situ, but is not reliable in low-grade tumors. Therefore, cystoscopy has remained the gold standard for surveillance after resection of bladder cancer. Recent data suggest that multi-target fluorescence in situ hybridization (FISH) can markedly improve the sensitivity of urinary cytology. The goal of this study was to investigate the utility of the recently developed FISH assay Uro-Vysion for the prediction of recurrence during surveillance. 134 bladder washes obtained during a negative follow-up cystoscopy from 127 patients were analyzed. Positive cytology was strongly associated with subsequent recurrence, emphasizing the importance of conventional cytology for bladder cancer surveillance. A positive UroVysion FISH test significantly predicted recurrence when cases with rare tetraploic cells were considered as negative. Taken together, both cytology and FISH help to better determine the risk of bladder cancer recurrence in order to establish more individualized follow-up schemes.

Cystoscopy↗
PubMed2003

Unenhanced helical computed tomography vs intravenous urography in patients with acute flank pain: accuracy and economic impact in a randomized prospective trial.

Unenhanced helical computed tomography (UHCT) has evolved into a well-accepted alternative to intravenous urography (IVU) in patients with acute flank pain and suspected ureterolithiasis. The purpose of our randomized prospective study was to analyse the diagnostic accuracy of UHCT vs IVU in the normal clinical setting with special interest on economic impact, applied radiation dose and time savings in patient management. A total of 122 consecutive patients with acute flank pain suggestive of urolithiasis were randomized for UHCT ( n=59) or IVU ( n=63). Patient management (time, contrast media), costs and radiation dose were analysed. The films were independently interpreted by four radiologists, unaware of previous findings, clinical history and clinical outcome. Alternative diagnoses if present were assessed. Direct costs of UHCT and IVU are nearly identical (310/309 Euro). Indirect costs are much lower for UHCT because it saves examination time and when performed immediately initial abdominal plain film (KUB) and sonography are not necessary. Time delay between access to the emergency room and start of the imaging procedure was 32 h 7 min for UHCT and 36 h 55 min for IVU. The UHCT took an average in-room time of 23 min vs 1 h 21 min for IVU. Mild to moderate adverse reactions for contrast material were seen in 3 (5%) patients. The UHCT was safe, as no contrast material was needed. The mean applied radiation dose was 3.3 mSv for IVU and 6.5 mSv for UHCT. Alternative diagnoses were identified in 4 (7%) UHCT patients and 3 (5%) IVU patients. Sensitivity and specificity of UHCT and IVU was 94.1 and 94.2%, and 85.2 and 90.4%, respectively. In patients with suspected renal colic KUB and US may be the least expensive and most easily accessable modalities; however, if needed and available, UHCT can be considered a better alternative than IVU because it has a higher diagnostic accuracy and a better economic impact since it is more effective, faster, less expensive and less risky than IVU. In addition, it also has the capability of detecting various additional renal and extrarenal pathologies.

Acute Disease↗
PubMed2002

[Manually-assisted laparoscopic donor nephrectomy].

The number of patients suffering from terminal renal failure awaiting kidney transplantation has continued to increase. Since the number of available cadaver donor kidneys has largely remained unchanged, a special publicity campaign achieved that almost one-half of the kidneys transplanted in Basle come from live donors. We performed a laparoscopic live donor nephrectomy in 14 patients between March 1998 and August 1999. Despite good experience regarding transplant function and patient satisfaction, the hand-assisted technique was introduced in 1999 because of the long average operating time of 230 min (200-270) and warm ischemia time of 7.5 min (4-9). In the 33 operations performed up to now, the average operating time and warm ischemia time could be significantly reduced to 185 min (135-240) and 2.4 min (1.5-4), respectively. Most recently, the technique of retroperitoneoscopic live donor nephrectomy was successfully employed in 4 patients and could possibly represent the method of choice for the future.

Adult↗
PubMed2001

ANX7, a candidate tumor suppressor gene for prostate cancer.

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.

Annexin A7↗
PubMed2001

Discovery of new DNA amplification loci in prostate cancer by comparative genomic hybridization.

BACKGROUND: DNA sequence amplifications are involved in the progression of many tumor types, and have also been found in advanced prostate cancer. The aim of this study was to detect new loci of DNA amplifications in prostate cancer. METHODS: Comparative genomic hybridization (CGH) was used for whole genome screening of DNA sequence copy number alterations in 27 advanced prostate cancers. RESULTS: The most prevalent changes were losses of 8p, 13q (52%, each), 6q (48%), 18q (37%), 5q (30%), 2q, 4q and 16q (26%, each), and gains of 8q (48%), Xq (40%), and Xp (26%). In addition, 16 high-level amplifications were found. These included Xq12 (five), 8q24 (two), and 11q13 (one) with known putative target genes (androgen receptor, MYC and Cyclin D1), and 1q21-25 (three), 10q22 (two), 17q23-24 (two), and 8q21 (one) where the target genes remain unknown. CONCLUSIONS: High-level amplifications at different chromosomal sites occur in advanced prostate cancer. The detection of amplified chromosomal regions may serve as a starting point to discover novel oncogenes involved in prostate cancer progression.

Aged↗
PubMed2001

Amplification of EIF3S3 gene is associated with advanced stage in prostate cancer.

Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease.

Aged↗
PubMed2001

Metastatic primitive neuroectodermal tumor of the kidney in adults.

OBJECTIVE: Primitive neuroectodermal tumors (PNET) of the kidney are rare and highly aggressive malignancies. The purpose of our study was to present information about the management of patients with metastatic disease. METHODS: The records of 2 patients (30-year-old female and 32-year-old male) with metastatic PNET of the kidney were reviewed and our data compared with the literature. RESULTS: Neither clinical evaluation nor radiological methods allowed to distinguish PNET from renal cell carcinoma. Immunohistochemistry revealed strong positivity for CD99 in tumor 1 and weak positivity for NSE and vimentin in both tumors. In tumor 2, EWS/FLI1 translocation was detected by RT-PCR. Patient 1 underwent nephrectomy, seven cycles of polychemotherapy, two cycles of high-dose chemotherapy, autologous bone marrow rescue, radiotherapy of suspicious skeletal foci and is without evidence of recurrent disease 28 months after therapy. Patient 2 underwent six cycles of polychemotherapy, nephrectomy, high-dose chemotherapy with cyclophosphamide and abdominal radiotherapy. Because of relapse high-dose chemotherapy with stem cell rescue was not performed. He underwent three further cycles of polychemotherapy and died one year after diagnosis due to cerebral metastasis. CONCLUSIONS: The diagnosis of renal PNET must be considered in young patients with renal neoplasm, particularly those with advanced disease at presentation. Achieving exact diagnosis has important clinical consequences because polychemotherapy and high-dose chemotherapy may lead to dramatic tumor reduction or even complete remission.

12E7 Antigen↗
PubMed2001

Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings.

The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL) fluorescence in situ hybridization (FISH) test for improved detection of bladder cancer in urinary specimens. Three groups of specimens were examined, including voided urine specimens (1) collected before resection of bladder cancer, (2) from cystoscopically negative bladders of patients with previous bladder cancer, and (3) from patients with benign prostatic hyperplasia (controls). FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The results were similar in a series of 68 bladder washings. In addition, FISH of voided urine specimens was positive in 5 of 10 patients with negative follow-up cystoscopy results. Subsequent recurrence was found in 4 of these patients but in none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves the sensitivity and specificity of cytology for the detection of bladder cancer in urine specimens.

Humans↗
PubMed2001

Molecular cytogenetic alterations associated with rapid tumor cell proliferation in advanced urinary bladder cancer.

Invasive urinary bladder carcinomas are characterized by a high number of cytogenetic alterations which are thought to pinpoint the location of critical genes, some of which may be involved in cell cycle control. To identify genomic alterations that may affect such genes the proliferative activity (Ki67 labeling index) was assessed in 93 invasively growing bladder carcinomas analyzed by comparative genomic hybridization. Only a few changes were significantly associated with rapid tumor cell proliferation, including 3p+ (p=0.0357), 6p+ (p=0.003), 8q+ (p=0.0273), and 11q- (p=0.0329). Among these alterations 6p+ is of particular interest because high level 6p22 amplifications occur frequently in bladder cancer. The particular strong association between 6p+ and a high tumor cell proliferation being independent of grade and stage suggests that a putative oncogene on 6p22 involved in cell cycle regulation.

Carcinoma, Transitional Cell↗