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Ruth Knüchel

Publications and source records attributed to Ruth Knüchel.

9 recordsLinked to original sources
PubMed2006

Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies.

BACKGROUND: Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of the secretoglobin superfamily, are known to be co-expressed in breast cancer, where their proteins form a covalent complex. Based on the relatively high tissue-specific expression pattern, it has been proposed that the mammaglobin A protein and/or its complex with lipophilin B could be used in breast cancer diagnosis and treatment. In view of these clinical implications, the aim of the present study was to analyze the expression of both genes in a large panel of human solid tumors (n = 309), corresponding normal tissues (n = 309) and cell lines (n = 11), in order to evaluate their tissue specific expression and co-expression pattern. METHODS: For gene and protein expression analyses, northern blot, dot blot hybridization of matched tumor/normal arrays (cancer profiling arrays), quantitative RT-PCR, non-radioisotopic RNA in situ hybridization and immunohistochemistry were used. RESULTS: Cancer profiling array data demonstrated that mammaglobin A and lipophilin B expression is not restricted to normal and malignant breast tissue. Both genes were abundantly expressed in tumors of the female genital tract, i.e. endometrial, ovarian and cervical cancer. In these four tissues the expression pattern of mammaglobin A and lipophilin B was highly concordant, with both genes being down-, up- or not regulated in the same tissue samples. In breast tissue, mammaglobin A expression was down-regulated in 49% and up-regulated in 12% of breast tumor specimens compared with matching normal tissues, while lipophilin B was down-regulated in 59% and up-regulated in 3% of cases. In endometrial tissue, expression of mammaglobin A and lipophilin B was clearly up-regulated in tumors (47% and 49% respectively). Both genes exhibited down-regulation in 22% of endometrial tumors. The only exceptions to this concordance of mammaglobin A/lipophilin B expression were normal and malignant tissues of prostate and kidney, where only lipophilin B was abundantly expressed and mammaglobin A was entirely absent. RNA in situ hybridization and immunohistochemistry confirmed expression of mammaglobin A on a cellular level in endometrial and cervical cancer and their corresponding normal tissues. CONCLUSION: Altogether, these data suggest that expression of mammaglobin A and lipophilin B might be controlled in different tissues by the same regulatory transcriptional mechanisms. Diagnostic assays based on mammaglobin A expression and/or the mammaglobin A/lipophilin B complex appear to be less specific for breast cancer, but with a broader spectrum of potential applications, which includes gynecologic malignancies.

Biomarkers, Tumor↗
PubMed2006

Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue.

The GABRP gene has been previously identified by in silico analysis of four million ESTs as a candidate gene differentially expressed in breast cancer. GABRP is located on chromosome 5q34 and it encodes the pi-subunit of the gamma-aminobutyric acid (GABA) receptor, a transmembrane protein expressed in the brain and several nonneuronal tissues. Using cDNA dot blot hybridisation (cancer profiling array), quantitative RT-PCR and non-radioisotopic in situ hybridisation (ISH), we have analysed GABRP expression in breast cancer and normal breast tissues as well as in nontumorigenic and tumorigenic breast cell lines. Analysis of the cancer profiling array revealed a more than 2-fold downregulation of GABRP (p < 0.001) in 76% of primary breast carcinomas (n = 50) compared to corresponding normal tissues. Quantitative RT-PCR in a panel of 23 normal human tissues showed that the GABRP expression level was most abundant in the normal breast tissues compared to other human tissues. GABRP downregulation in breast cancer was confirmed by quantitative RT-PCR in cryopreserved breast tumour and normal breast tissue specimens (n = 22), in archival formalin-fixed, paraffin-embedded tissue specimens (n = 32), as well as in breast cancer cell lines (n = 8). Furthermore, a significant downregulation of GABRP was noted in large (pT3-pT4) (p = 0.044) primary breast tumours. Non-radioisotopic ISH showed strong GABRP expression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.

Breast↗
PubMed2005

Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study.

PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL) fluorescence cystoscopy could lead to improved treatment in patients with bladder cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected bladder cancer were assessed in this open, comparative, within patient, controlled phase III study. Patients received intravesical HAL for 1 hour and were assessed with standard white light cystoscopy and blue light fluorescence cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken from suspicious areas for assessment by an independent pathologist. An independent urologist blinded to the detection method used recommended treatment plans based on biopsy results and medical history according to European Association of Urology bladder cancer guidelines. Any differences in recommended treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL imaging improved overall tumor detection. Of all tumors 96% were detected with HAL imaging compared with 77% using standard cystoscopy. This difference was particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs 68%) and superficial papillary tumors (96% vs 85%). As a result of improved detection, additional postoperative procedures were recommended in 15 patients (10%) and more extensive treatment was done intraoperatively in a further 10. Overall 17% of patients received more appropriate treatment at the time of the study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective than standard white light cystoscopy for detecting bladder tumors and lesions. This leads to improved treatment in a significant number of patients (p <0.0001).

Administration, Intravesical↗
PubMed2005

Diagnosis of urothelial carcinoma of the bladder using fluorescence endoscopy.

Bladder cancer is a frequent disease and represents the second most common genitourinary neoplasm. Although many aspects of the management of superficial bladder cancer are now well established, significant challenges remain, which influences patient outcome. Early detection and treatment of recurrent disease is required to optimize bladder preservation, reduce patient morbidity, and increase quality of life and survival. Fluorescence endoscopy, often referred to as 'photodynamic diagnosis' (PDD), with intravesical application of photosensitizing agents, has been developed to enhance the early detection of bladder cancer. There is growing evidence that PDD using 5-aminolaevulinic acid (ALA), hexyl-ALA ester or hypericin enhances the detection of bladder cancer, particularly of high-grade flat lesions. Furthermore, transurethral resection of bladder tumour under fluorescence guidance reduces the risk of recurrent tumours. However, the impact on the progression of disease remains unclear and must be investigated in prospective randomized trials.

Aminolevulinic Acid↗
PubMed2004

Hexaminolevulinate-induced fluorescence endoscopy in patients with rectal adenoma and cancer: a pilot study.

BACKGROUND: Fluorescence endoscopy is a promising new method for detection and treatment of premalignant and malignant lesions. The aim of this pilot study was to investigate the feasibility of hexaminolevulinate-based photodetection of rectal adenoma and cancer, including safety, dose finding, and efficacy. METHODS: Ten patients with known rectal adenoma or cancer were sensitized by instillation of 3.2 mM of hexaminolevulinate as an enema. Fluorescence endoscopy was performed after retention of the enema for 30 to 60 minutes, followed by a rest time of up to 30 minutes before endoscopy. Biopsy specimens were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to assess the distribution of protoporphyrin IX fluorescence in different tissue layers. Adverse events were reported by direct questioning of all patients; skin photosensitivity, changes in biochemical tests of liver function, blood pressure and heart rate, and the occurrence of GI symptoms (nausea, vomiting) were recorded for 5 patients. OBSERVATIONS: Hexaminolevulinate-induced fluorescence endoscopy produced selective fluorescence of all rectal adenomas with intraepithelial neoplasia. For rectal cancer, there was only weak fluorescence or none at all. No hexaminolevulinate-induced side effect was observed. In two patients, fluorescence differentiated adenomas and hyperplastic polyps. CONCLUSIONS: Hexaminolevulinate-based fluorescence endoscopy (3.2 mM administered as an enema) in patients with rectal cancer and adenoma was well tolerated and produced no significant skin sensitivity or other side effects. The optimal duration of application is 30 to 45 minutes, with a rest time of 30 minutes. Selective fluorescence of adenoma with intraepithelial neoplasia suggests that hexaminolevulinate-based fluorescence endoscopy may be useful for detection of premalignant lesions.

Adenoma↗
PubMed2004

Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - in vivo experiments on the dunning rat tumor model.

OBJECTIVE: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) in an in vivo tumor model. METHODS: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques. Thereafter, PDT using 150 mg 5-ALA/kg b.w. i.v. was performed by homogenous irradiation of the photosensitized tumor (diode laser lambda = 633 nm). The tumors were resected 2 days post-PDT and the extent of the necrosis was determined histopathologically. RESULTS: The kinetics of PPIX fluorescence revealed a maximum intensity in the tumor tissue within 3 and 4.5 h post-application of 5-ALA. At this time, specific PPIX fluorescence could be localized selectively in the tumor cells. The PDT-induced necrosis (n = 18) was determined to be 94 +/- 12% (range 60-100%), while the necrosis of the controls (n = 12) differs significantly (p < 0.01), being less than 10%. CONCLUSION: These first in vivo results demonstrate the effective potential of 5-ALA-mediated PDT on PCA in an animal model.

Aminolevulinic Acid↗
PubMed2004

Detection of dysplastic lesions by fluorescence in a model of chronic colitis in rats after local application of 5-aminolevulinic acid and its esterified derivatives.

5-Aminolevulinic acid (ALA) and ALA ester-induced protoporphyrin IX (PPIX) fluorescence are used for photodynamic diagnosis and therapy with promising results. The aim of the present study was to investigate the detection of dysplastic lesions by fluorescence after topical application of ALA and different esterified derivatives in a model of chronic colitis in rats. In female CD rats chronic colitis was induced by oral application of 5% dextrane sulfate sodium. ALA was used at different concentrations (0.072 and 0.036 mol/L). ALA-methylester (m-ALA), ALA-hexylester (h-ALA) and ALA-benzylester (b-ALA) were used at a concentration of 0.003, 0.002 and 0.002 mol/L, respectively. Fluorescence was examined under blue light, and histological findings of fluorescent and nonfluorescent biopsy specimens were recorded. Using ALA at a concentration of 0.072 mol/L, all dysplastic lesions (8/8) showed fluorescence (sensitivity 100%). Specificity was low at 57%. Reducing the concentration to 0.036 mol/L resulted in a sensitivity of only 56% (5/9) with an increase in specificity to 76%. On using h-ALA, sensitivity was 60% (3/5) with a specificity of 51%. Using m-ALA and b-ALA, sensitivity values were 25% and 33%, and values for specificity were 62% and 63%, respectively. Despite a low number of dysplastic lesions, the results of this study indicate that ALA ester-induced PPIX fluorescence has the potential for the detection of premaligant lesions but was not superior to ALA. ALA esters were used in 18- to 36-fold lower concentrations compared with ALA.

Administration, Topical↗
PubMed2003

Synovial sarcoma--unusual presentation with cerebral hemorrhage.

INTRODUCTION: Soft-tissue sarcomas account for 1% of all malignancies in adults. Typical symptoms comprise a growing and painless mass. Occasionally, the diagnosis is facilitated by secondaries. MATERIALS AND METHODS: Here we report the first case presented with intracranial hemorrhage caused by a metastasis of a previously unknown synovial sarcoma. The 74-year-old female patient was under anticoagulation for recurrent thrombosis of the right popliteal vein due to compression by the sarcoma, misdiagnosed as Baker's cyst. The brain metastasis was resected, and after an incisional biopsy of the suspected tumor, which confirmed the diagnosis of a synovial sarcoma, an above knee amputation was performed because of the invasion of the neurovascular structures in the popliteal fossa. RESULTS: The patient died 11 months after the initial event from pulmonary and further brain metastases. CONCLUSION: Brain metastases are seldom the primary factor in the management of advanced synovial sarcoma. Initially, the primary tumor was thought to be a benign cyst; we therefore recommend a biopsy/excision of lesions greater than 5 cm in size and with growth tendency to allow appropriate treatment.

Aged↗