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W Brenner

Publications and source records attributed to W Brenner.

At least 19 recordsLinked to original sources
PubMed2004

Sentinel lymph-node biopsy in head and neck cancer.

The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.

Carcinoma, Squamous Cell↗
PubMed2002

Downregulation of beta2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?

Adherently growing, non-hematopoietic somatic stem cells isolated from human cord blood were stained with the fluorescent dye PKH26 and transplanted into livers of SCID-mice to examine a possible cell fate transition. Already 7 days after transplantation stem cells were well integrated into the liver tissue. Human albumin that was not expressed by the stem cells before transplantation was detectable in the host's livers after injection of cord blood stem cells. Human alpha1-antitrypsin was detectable in stem cells already before transplantation and remained positive in the mouse liver. The most interesting observation in this study was the downregulation of human beta2-microglobulin (beta2M) in the stem cells after transplantation: beta2M is expressed constitutively in our cord blood stem cells. However, beta2M was no longer detectable by RT-PCR in all tissues where human albumin and alpha1-antitrypsin were expressed after stem cell transplantation. beta2M is known to participate as an integral part of the major histocompatibility complex. Absence of beta2M makes the residual heavy chain inactive as an antigen. Thus, downregulation of beta2M may represent an escape mechanism from killer-T cells and may be a molecular mechanism explaining the recently described "immunological blindness" [37] of stem cells. In contrast to the results obtained after direct injection of stem cells as a suspension, no consistent downregulation of beta2M was observed after transplantation of stem cells encapsulated in alginate beads to generate a compartment where stem cells are protected from the host's natural killer cells. No expression of human genes was observed after transplantation of human cord blood derived mononuclear cells (MNC) that were used as a negative control. In conclusion, we have shown that human cord blood somatic stem cells survive and are reprogrammed after transplantation into mouse livers, although a complete transdifferentiation to hepatocytes did not occur within 7 days, since some marker genes (GATA4 and alpha-fetoprotein) were still negative. Switching off expression of beta2M may be part of an intriguing and novel mechanism explaining why stem cells escape the host's immune system.

Aged↗
PubMed2001

Mandibular reconstruction with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: an experimental study in miniature pigs. Part II: transplantation.

Osteogenic Protein-1 (rhOP-1), also called bone morphogenetic protein-7 (BMP-7), is osteoinductive. The aim of this study was to present a new surgical technique: the prefabrication of a vascularized bone graft using rhOP-1 and its microsurgical transplantation. During 6 weeks, osteomuscular grafts were prefabricated in the latissimus dorsi muscle of five adult minipigs. Six hundred micrograms rhOP-1 on a carrier of xenogenic bone mineral in block form were used. The grafts were transplanted into defects of the mandibular angles performing a microsurgical anastomosis and using miniplates for fixation. Identical defects of the contralateral side were treated by direct application of 600 microg rhOP-1 and xenogenic bone mineral. A polychrome sequential labelling was applied. After transplantation the bone stayed viable, demonstrated by continuous apposition of fluorochromes (non-decalcified histologic sections) and bone scintigraphy. The reconstructive result was significantly superior in the prefabrication technique, assessed by histology and computerized tomography (CT). In conclusion, the method has a potential to become a clinical alternative for conventional vascularized bone grafts.

Anastomosis, Surgical↗
PubMed2001

Long-term results of radiation synovectomy: a clinical follow-up study.

Radiation synovectomy by intra-articular injection of beta-emitting radionuclides is a reliable and easy-to-perform therapy without harmful side effects for the treatment of inflammatory rheumatoid as well as degenerative joint diseases. The indication for radiation synovectomy is based on both clinical symptoms and on proven hyperperfusion, with active synovitis being seen on a pre-therapeutic three-phase bone scan. In this study, the clinical response after 6-18 months, evaluated by a standardized questionnaire, was compared with the reduction of synovitis seen on three-phase bone scintigraphy after treatment of 475 joints in 151 patients. The best clinical results were obtained in cases of true rheumatoid arthritis (73.4%), with less in other kinds of arthritis (48.8%) such as psoriatic or reactive arthritis. Because of the inflamed synovium being the main target tissue, clinical results in osteoarthritis with severe bone destruction are poorer (33.9%). However, synovitis can be markedly reduced (in approximately 70%), regardless of the underlying diagnosis, as shown by post-therapeutic three-phase bone scanning. Radiation synovectomy can be recommended in all kinds of arthritis. It should also be considered in cases of osteoarthritis as a last therapeutic option prior to joint replacement.

Adult↗
PubMed2001

Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.

Adenocarcinoma, Clear Cell↗
PubMed2001

Skeletal uptake and soft-tissue retention of 186Re-HEDP and 153Sm-EDTMP in patients with metastatic bone disease.

UNLABELLED: The aim of this study was to introduce a new quantification method for 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) and 186Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to separately measure bone uptake and soft-tissue retention of these radiopharmaceuticals. METHODS: Studies were performed on 23 men and 6 women undergoing radionuclide therapy for palliation of bone pain. Whole-body images were acquired at 3 min, 3-4 h, and 24-72 h after injection of 1,295 MBq 186Re-HEDP and 37 MBq 153Sm-EDTMP per kilogram of body weight. The activities for whole body, urinary bladder, and both thighs, as representative of soft tissue, were measured by region-of-interest technique. A background region of interest adjacent to the head was used to correct for bremsstrahlung. Bone uptake was calculated as initial whole-body activity minus urinary excretion and remaining soft-tissue activity. RESULTS: For 186Re-HEDP (n = 11) the mean bone uptake at 3 h after injection was 13.7% +/- 8.6% of initial whole-body activity. The remaining soft-tissue activity was 49.4% +/- 16.9%, and urinary excretion was 36.9% +/- 14.4%. At 24 h after injection, bone uptake reached a value of 21.8% +/- 9.0%. Urinary excretion increased to 65.3% +/- 12.8% according to a decreasing soft-tissue remainder activity of 12.8% +/- 5.4%. The corresponding results for 153Sm-EDTMP (n = 18) at 3 h after injection were 29.2% +/- 15.5% for bone uptake, 32.3% +/- 12.9% for urinary excretion, and 38.4% +/- 14.5% for soft tissue. At 24 h after injection, we calculated values of 47.7% +/- 11.2% for bone uptake, 39.5% +/- 13.8% for urinary excretion, and 12.7% +/- 4.7% for soft tissue. CONCLUSION: Bone uptake and soft-tissue retention for both 186Re-HEDP and 153Sm-EDTMP as obtained in this study agree well with the conventional 24-h whole-body retention measurements for these tracers. However, by this new scintigraphic quantification method, bone uptake and soft-tissue retention can be calculated separately, thus providing more detailed kinetic data and potentially improving the dosimetry of these radiopharmaceuticals in, for example, assessment of radiation dosage to bone and bone marrow.

Aged↗
PubMed2001

High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model.

UNLABELLED: The aim of this experimental study was to investigate the myeloprotective potential of amifostine in rabbits receiving high-dose treatment with either (153)Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or (186)Re-hydroxyethylidene diphosphonate (HEDP) and to check for drug interactions impairing the skeletal uptake of these radiopharmaceuticals by amifostine. METHODS: To a total of 24 rabbits, we administered 1,000 MBq of either (153)Sm-EDTMP (n = 12) or (186)Re-HEDP (n = 12). Six animals of each group received 500 mg amifostine intravenously 10-15 min before injection of the radiopharmaceutical, whereas the other 6 animals served as controls. Up to 8 wk after treatment, blood samples were collected every 3-5 d to measure platelet and leukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h, and 24 h after injection of the radiopharmaceutical to quantify the skeletal uptake. RESULTS: For (186)Re-HEDP, the mean decrease in platelets was significantly less in the amifostine group (35.5% +/- 2.4%) than in the control group (61.3% +/- 5.4%, P < 0.001). Similar results were found for (153)Sm-EDTMP (36.5% +/- 8.3% vs. 52.3% +/- 14.0%, P < 0.05). No significant differences in leukocyte counts were found for (186)Re-HEDP (75.3% +/- 12.3% in the amifostine group and 72.5% +/- 4.1% in the control group, P > 0.05), whereas rabbits treated with (153)Sm-EDTMP plus amifostine showed a significantly greater decrease in leukocytes (69.2% +/- 10.8%) than did the control group (56.6% +/- 4.0%, P < 0.05). Bone uptake in percentage of initial total whole-body activity was significantly decreased in animals treated with amifostine compared with the control groups for both (186)Re-HEDP (15.8% +/- 3.1% vs. 30.9% +/- 1.9%, P < 0.001) and (153)Sm-EDTMP (31.7% +/- 8.9% vs. 44.0% +/- 6.5%, P < 0.05). CONCLUSION: For amifostine, we found a highly significant cytoprotective effect on platelets but no leukoprotective effect. The latter probably relies on the intrinsic myelotoxicity of high-dose amifostine, which seemed to potentiate the leukodepression of the radiopharmaceuticals. The lower bone uptake in amifostine-treated animals may be caused by the chemical structure of amifostine, which is a potentially complex-forming compound that may be able to displace bisphosphonates from the rhenium- and samarium-bisphosphonate complexes, resulting in altered biodistribution patterns.

Amifostine↗
PubMed2000

Differential inhibition of renal cancer cell invasion mediated by fibronectin, collagen IV and laminin.

Invasion of tumor cells into the extracellular matrix is an essential step in the formation of metastases in renal cancer. Cell adhesion molecules such as beta(1)-integrins, which bind to the RGD sequence (arginine-glycine-asparagine) and CD44 are involved in this process. We examined the invasion of a renal carcinoma cell line (CCF-RC1) into the extracellular matrix compounds fibronectin, collagen IV and laminin and the effect of TGFbeta and IFNgamma on this process. The inhibitory effect of an antibody against the beta(1)-subunit of integrins (CD29), as well as a pentapeptide including the RGD sequence, was also evaluated. A micro-chemotaxis chamber, including a polycarbonate membrane with a pore diameter of 8 microm, was used for quantification of cell migration. The addition of the extracellular matrix compounds fibronectin, laminin and collagen IV resulted in a 5-10-fold increase in invasion. This increased invasion depends strongly on the presence of beta(1)-integrins, shown by the use of an antibody against CD29 or a RGD including peptide which inhibit the cell migration by approximately 88%. CD44 is less involved in collagen IV dependent migration and almost no influence of CD44 was observed on a fibronectin and laminin dependent migration. TNFalpha and IFNgamma did not significantly influence the expression of CD29 or CD44, and no alteration in tumor cell migration was observed. These results show that the invasion of renal cancer cells is differentially regulated by compounds of the extracellular matrix, whereby fibronectin seems to be the most critical factor. The molecular interactions in this process are strongly dependent on beta(1)-integrins and the corresponding amino acid sequence RGD.

Carcinoma, Renal Cell↗
PubMed2000

VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation.

To elucidate the role of somatic alterations for renal cancer etiology and prognosis, we analyzed 227 sporadic renal epithelial tumors for mutations and hypermethylations in the von Hippel-Lindau tumor suppressor gene VHL. Tumors were classified according to the recommendations of the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Somatic VHL mutations were identified by PCR, single-strand conformation polymorphism analysis, and sequencing, and hypermethylations were identified by restriction enzyme digestion and Southern blotting. Frequencies of VHL alterations were established, and an association with tumor type or tumor type and tumor stage was evaluated. VHL mutations and hypermethylations were identified in 45% of clear cell renal cell carcinomas (CCRCCs) and occasionally (3 of 28) in papillary (chromophilic) renal cell carcinomas (RCCs). Lack of VHL mutations and hypermethylations in chromophobe RCCs and oncocytomas was statistically significant (P = 0.0001 and P = 0.0004, respectively). RCCs carrying VHL alterations showed, in nine cases (12%), mutations at a hot spot involving a thymine repeat (ATT.TTT) in exon 2. Tumor staging was critical to the VHL mutation/hypermethylation detection rate in CCRCCs shown by separate evaluation of patients from medical centers in Munich, Heidelberg, and Mainz. The spectrum of pT1, pT2, and pT3 CCRCCs and the VHL mutation/hypermethylation detection rate varied among these three groups. Altogether, VHL alterations were significantly associated with pT3 CCRCCs (P = 0.009). This is the first evidence of frequent somatic VHL mutations at a particular site within exon 2 and an association of VHL mutations/hypermethylations with a standard prognostic factor.

Adenoma, Oxyphilic↗
PubMed2000

[Lymph scintigraphy and pre- and intraoperative gamma probe measurements for localization of sentinel lymph nodes (SLN) in breast cancer].

UNLABELLED: Aim of this study was to prove the clinical value of nuclear medicine procedures to detect the sentinel lymph node (SLN) for SLN biopsy. METHODS: In 132 patients with breast cancer we performed lymph scintigraphy of the breast as well as both pre- and intraoperative gamma probe measurements correlating the results with the findings of histopathology. RESULTS: SLN were detectable in 62 of 110 patients according to a sensitivity of 56% when scanning was performed only at 1-2 h p.i. while the sensitivity increased to 86% (19 of 22 pts.) if sequential images were acquired up to 2 h p.i. One or more SLN were identified by a hand-held gamma probe transcutaneously prior to surgery in 96% (113 of 118 pts.) of the patients who showed up with no clinically suspected lymph node metastases. Intraoperatively, in additionally 2 patients the SLN could be found resulting in a sensitivity of 97% (115 of 118 pts.). In only 3 patients with clinically no tumor spread to axillary lymph nodes no SLN could be identified by the probe. Skip lesions, i.e. lymph node metastases in patients with tumor-free SLN, occurred in 2 cases: due to SLN biopsy in these patients lymph node staging was false negative compared to conventional staging by means of axillary lymph node dissection. CONCLUSION: The results demonstrate a high preoperative detection rate of SLN in patients with breast cancer using lymph scintigraphy and gamma probe measurements. Thus, nuclear medicine is capable of providing the basic requirements for SLN biopsy in the daily routine.

Adult↗
PubMed2000

Age- and sex-related bone uptake of Tc-99m-HDP measured by whole-body bone scanning.

UNLABELLED: AIM of this study was to validate a recently introduced new and easy-to-perform method for quantifying bone uptake of Tc-99m-labelled diphosphonate in a routine clinical setting and to establish a normal data base for bone uptake depending on age and gender. METHODS: In 49 women (14-79 years) and 47 men (6-89 years) with normal bone scans as well as in 49 women (33-81 years) and 37 men (27-88 years) with metastatic bone disease whole-body bone scans were acquired at 3 min and 3-4 hours p.i. to calculate bone uptake after correction for both urinary excretion and soft tissue retention. RESULTS: Bone uptake values of various age-related subgroups showed no significant differences between men and women (p > 0.05). Furthermore, no differences could be proven between age-matched subgroups of normals and patients with less than 10 metastatic bone lesions, while patients with wide-spread bone metastases revealed significantly increased uptake values. In both men and women highest bone uptake was obtained (p < 0.05) in subjects younger than 20 years with active epiphyseal growth plates. In men, bone uptake slowly decreased with age up to 60 years and then showed a tendency towards increasing uptake values. In women, the mean uptake reached a minimum in the decade 20-29 years and then slowly increased with a positive linear correlation of age and uptake in subjects older than 55 years (r = 0.57). CONCLUSION: Since the results proposed in this study are in good agreement with data from literature, the new method used for quantification could be validated in a large number of patients. Furthermore, age- and sex-related normal bone uptake values of Tc-99m-HDP covering a wide range of age could be presented for this method as a basis for further studies on bone uptake.

Adolescent↗
PubMed2000

Radiation exposure to the personnel in the operating room and in the pathology due to SLN detection with Tc-99m-nanocolloid in breast cancer patients.

UNLABELLED: AIM of this study was to assess the radiation exposure for the personnel in the operating room and in the pathology laboratories caused by radioguided SLN localization in breast cancer. METHODS: In 15 patients dose rates were measured at various distances from the breast and tumor specimens during operation and pathological work-up at 3-5 h after peritumoral injection of 30 MBq Tc-99m-nanocolloid. RESULTS: The dose rates were 84.1 +/- 46.4 microGy/h at 2.5 cm, 3.57 +/- 2.14 microGy/h at 30 cm, 0.87 +/- 0.51 microGy/h at 100 cm, and 0.40 +/- 0.20 microGy/h at 150 cm in the operating room and 44.4 +/- 27.8 microGy/h at 2.5 cm, and 1.66 +/- 1.34 microGy/h at 30 cm in the pathology laboratories. From these data the radiation exposure was calculated for 250 operations per year assuming a mean exposure time of 30 min for the surgical team members and of 10 min for the pathology staff. Under these conditions the finger dose is 10.5 mGy for the surgeon, and 5.55 mGy for the pathologist. The whole-body doses are 0.45 mSv, 0.11 mSv, 0.05 mSv, and 0.21 mSv for the surgeon, the operating room nurse, the anesthetist, and the pathologist, respectively. CONCLUSION: Since the radiation risk to staff members is low, a classification of the personnel in the operating room and in the pathology laboratories as occupational radiation exposed workers is not necessary.

Breast Neoplasms↗
PubMed1999

Enhanced expression of ELAM-1 on endothelium of renal cell carcinoma compared to the corresponding normal renal tissue.

Renal cell carcinoma (RCC) has been shown to respond to an immunological therapy with tumor infiltrating lymphocytes (TIL), which accumulate in RCC at a higher density than in normal renal tissue, suggesting that there is selective tumor invasion. Since invasion of TIL into the malignant tissue is mediated by adhesion molecules, we examined the different expression of the adhesion molecule endothelial-leukocyte-adhesion-molecule-1 (ELAM-1) on endothelial cells of RCC versus normal renal tissue. For a specific quantification, the level of ELAM-1 mRNA was investigated by both semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis and referred to the content of endothelial cells in the tissue, determined by endothelium specific staining. Quantification of mRNA was evaluated by computer-aided integration. We observed a significantly lower amount of endothelial cells in RCC compared to normal renal tissue. The specific transcription rate of ELAM-1 in RCC, determined by RT-PCR was about 5.2 times that of normal tissue, while Northern blot analysis indicated an approximately 11.8 times increase. Our investigations show a significantly increased expression of ELAM-1 in tumor tissue compared to normal renal tissue, presumably caused by a higher amount of cytokines in the tumor tissue. This enhanced expression may be responsible for the high concentration of TIL in renal tumors.

Blotting, Northern↗