Do modifications of nonequimolar assays for total prostate-specific antigen improve detection of prostate cancer?
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Aged↗
Biomedical subjects
B Brandt
Publications and source records attributed to B Brandt.
[Pharmacologic stimulation of ejaculation with midodrine hydrochloride (Gutron) for medically assisted reproduction in spinal injury].
INTRODUCTION: Midodrine hydrochloride (Gutron) is proposed to induce ejaculation in spinal injury patients desiring paternity as an alternative to vibromassage, electrostimulated ejaculation and surgical collection of spermatozoa. The authors report their experience in 10 spinal injury patients. PATIENTS AND METHODS: 14 trials of pharmacologically-induced ejaculation were performed in a context of medically assisted reproduction (MAR) in 10 spinal injury patients (7 with paraplegia > T11; 1 with paraplegia < or = T11; 2 with quadriplegia) an average of 4.5 years after the injury. Patients had a mean age of 28.5 years (range: 18 to 36 years). Nine had persistent reflex erections. After IC injection of prostglandin E, 10 to 30 mg of Gutron was administered by slow i.v. infusion. Spermatozoa were collected during antegrade ejaculation and/or in previously alkalinised urine. RESULT: Ejaculation was obtained in 10 cases (71.4%), either antegrade (7 cases), or retrograde (3 cases). The 4 failures corresponded to ejaculation failure in 3 cases and adverse effects of Gutron (hypertension) in 1 case. However, storage of spermatozoa could be performed in only 4 cases (40%), as pyospermia or severe necrospermia were observed in 6 cases. CONCLUSIONS: Midodrine hydrochloride gives good results in terms of ejaculation in spinal injury patients. However, the quality of semen collected is often poor due to the long interval since the initial trauma. Midodrine hydrochloride, ideally used after antibiotic treatment, can nevertheless constitute an alternative to other techniques.
Adolescent↗
Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo.
Overexpression of the ErbB2 and epidermal growth factor receptor (EGFR) tyrosine kinases is frequently observed in squamous cell carcinomas of the head and neck, and has been correlated with shorter overall survival. By immunoblot analysis, we have found EGFR and ErbB2 expression in 6 out of 6 established head and neck cancer cell lines. Elevated EGFR protein levels were noted in 3 and elevated ErbB2 levels in 5 of them. Significant expression of EGFR and ErbB2 was also detected in 17 of 47 and 26 of 45 primary tumor samples. Due to their enhanced expression on the tumor cell surface, these receptors can be regarded as suitable targets for directed cancer therapy. We have analyzed the antitumoral activity of recombinant single-chain antibody toxins specific for ErbB2 and EGFR against head and neck cancer cells in vitro and in vivo. The recombinant toxins consist of the variable domains of the heavy and light chains of monoclonal antibodies (MAbs) genetically fused to a truncated Pseudomonas exotoxin A (ETA). At low concentrations, the ErbB2-specific single-chain antibody (scFv) toxin scFv(FRP5)-ETA and the EGFR-specific toxins scFv(225)-ETA and scFv(14E1)-ETA inhibited the in vitro growth of established head and neck cancer cell lines and primary tumor cells. In a nude mouse tumor model, intratumoral injection of the antibody toxins resulted in the rapid regression of subcutaneously growing CAL 27 tumor xenografts, with scFv(FRP5)-ETA and scFv(14E1)-ETA treatment being most effective and leading to the cure of up to 50% of the animals. Our results suggest that EGFR and ErbB2-specific antibody toxins may become valuable therapeutic reagents for the treatment of squamous cell carcinomas of the head and neck.
ADP Ribose Transferases↗
Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression.
Overexpression of epithelial growth factor receptor (EGFR) is correlated with a poor prognosis and reduced steroid receptor expression. Recently, it was demonstrated that the length of a CA repeat in the intron 1 of EGFR correlated with the expression of EGFR in vitro. We investigated 112 cases of cancerous and noncancerous breast tumor samples for loss of heterozygosity (LOH) in intron 1 of the egfr gene and determined the intratumoral EGFR content and genetic alterations by comparative genomic hybridization. Heterozygous tumors with short CA repeats showed elevated EGFR expression in contrast to tumors with longer CA repeats. Tumors with LOH in intron 1 of egfr revealed higher EGFR expression when the longer allele was lost compared with loss of the shorter allele. Additionally, tumors with a loss of the long allele showed more chromosomal alterations, especially a higher frequency of amplifications. We conclude that the CA repeat status in intron 1 of the egfr gene also modulates the intratumoral EGFR content in vivo. Furthermore, LOH at the CA repeat is associated with genetically advanced tumors. Therefore, allele-specific gene expression due to LOH of the CA repeat could be assumed to be an important event in invasive breast cancer development.
Alleles↗
[From antigen to tumor marker. Results of research regarding PSA and its clinical applications].
The determination of prostate-specific antigen is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and current status of prostate-specific antigen in tumor diagnostics.
Biomarkers, Tumor↗
Clinical relevance of erbB-1 and -2 oncogenes in oral carcinomas.
To gain a better understanding of molecular changes in oral squamous cell carcinomas, we tested fresh tumour specimens from 110 patients for erbB-1 and -2 oncogene aberrations using the competitive differential polymerase chain reaction. The significance of established tumour characteristics such as TNM stage, differentiation and oncogene aberrations for tumour progression were analyzed. ErbB-2 amplification with a gene copy number > 1.6 in tumour tissue and erbB-1 deletion with a gene copy number < 0.4 in tumour-surrounding mucosa are of clinical relevance and indicate an early tumour recurrence or metastasis (p < 0.05). In T1/T2 tumours an erbB-2 gene dosage study allows differentiation between tumours with high or low risk for early progression. In a multivariate statistical analysis T stage (p < 0.01) and erbB-2 amplification in tumour material (p < 0.05) were independent prognostic variables.
Adult↗
Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use.
AIMS: This study was performed to test the validity of different methods for determining the status of the erbB-2/HER-2 oncogene in breast cancer tissues for diagnostic use. METHODS AND RESULTS: Forty formalin-fixed, paraffin-embedded breast carcinomas were investigated by fluorescence in situ and comparative genomic hybridization (FISH, CGH) as well as by immunohistochemistry (IHC) using Dako-HercepTest and CB11 antibody (Ventana). Additionally, competitive-differential polymerase chain reaction (cdPCR) was performed on frozen samples to estimate gene dosage alterations of erbB-2/HER-2. Amplification was detected in 12-23% and protein overexpression in 16-68% of the cases, depending on the methodology and/or the reagent used. Perfect concordance (100%) was found between the results of cdPCR and CB11-IHC, and a 97% concordance between FISH and CB11-IHC. The concordance between Dako-HercepTest and CB11-IHC was 78%: seven of eight 2+ carcinomas with the Dako-HercepTest were classified as nonamplified using FISH. CONCLUSIONS: Our results indicate that high-level expression as well as normal erbB-2/HER-2 status of breast carcinomas can be detected reliably both by IHC and gene dosage assessment in paraffin material for diagnostic use. However, borderline results, especially those with 2 + immunopositivity, should be interpreted with caution and increased emphasis should be given to other clinical and prognostic information available.
Adenocarcinoma↗
The clinical impact of different assays for prostate specific antigen.
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Humans↗
Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer.
The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.
Adenocarcinoma↗
Modulation of EGFR gene transcription by secondary structures, a polymorphic repetitive sequence and mutations--a link between genetics and epigenetics.
The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation and motility of normal as well as tumor cells. The transduction of extracellular signals to the cytoplasm via the receptor not only depends on ligand binding, but is also determined by the receptor density on the cell surface. Therefore, in terms of cancer diagnosis and therapeutic approaches targeting EGFR it is decisive to know how the expression level of EGFR is controlled. We found that transcription activity declines with increasing numbers of CA dinucleotides of a highly polymorphic CA repeat in the first intron epidermal growth factor receptor gene. In vivo data from cultured cell lines support these findings, although other regulation mechanisms can compensate this effect. In addition, we showed that RNA elongation terminates at a site closely downstream of the simple sequence repeat (SSR) and that there are two separate major transcription start sites. Model calculations for the helical DNA conformation revealed a high bendability in the EGFR polymorphic region, especially if the CA stretch is extended. These data suggest that the CA-SSR can act like a joint bringing the promoter in proximity to a putative repressor protein bound downstream of the CA-SSR. The data suggest that this polymorphism is a marker for cancer linking genetic and epigenetic risk. Furthermore in breast cancer, heterozygous tumours with short CA-SSR showed an elevated EGFR-expression in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in intron 1 of egfr revealed an increased EGFR expression if the longer allele was lost. Moreover, deceased egfr gene dosages were significantly correlated to poor prognosis in breast cancer.
Animals↗
[Treatment of female stress urinary incontinence with cystocele by Gore Tex colpofixation and Burch operation].
OBJECTIVE: We treat female urinary stress incontinence (USI) with cystocele with or without associated genital prolapse by a combination of sacral colpopexy and Burch anterior colposuspension. We evaluated the results of a consecutive series of 77 patients completing a telephone interview after a mean follow-up of 40.6 months (range: 15 to 74 months). MATERIAL AND METHODS: From January 1991 to December 1995, 77 patients (mean age: 56.7 years) underwent Gore-Tex sacral colpopexy and Burch colposuspension for USI. Levator ani myorrhaphy was also performed in 53 severe cases. Incontinence was severe in every case, and associated with stage > or = 2 cystocele in 93% of cases. Urodynamic assessment revealed detrusor instability (DI) in 17.3% of cases and sphincter insufficiency (SI) < or = 35 cm H2O in 11.9% of cases. The main complications were: 4 haemorrhages requiring transfusion of one unit, 2 wound abscesses, one wall haematoma, and one small bowel obstruction at the 4th month, treated surgically. RESULTS: Six patients were lost to follow-up (good early results) and 2 files could not be analysed with sufficient follow-up (patients died from other diseases). Good results were defined by at least two of the following criteria: patient satisfied, no incontinence and no need for protective pads. We obtained 59 successes (85.5%) and 10 failures (14.5%). The results remained stable over time with 88.8% of success after a follow-up of more than 60 months (20 patients). Nine of the 10 failures occurred during the first year. They were demonstrated by the survey, while the post-operative follow-up at one month had been satisfactory. No specific treatment was therefore proposed. The two main factors of failures were DI and severe SI. Three times more failures were observed when the preoperative closure pressure were less than 30 cm H2O. CONCLUSION: Sacral colpopexy combined with Burch operation is a reliable solution for repair of USI with marked cystocele. It ensures good initial results which persist at one year and in the long-term.
Adult↗
Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1.
The influence of a highly polymorphic CA dinucleotide repeat in the epidermal growth factor receptor (EGFR) gene on transcription was examined with a quantitative nuclear run-off method. We could demonstrate that transcription of the EGFR gene is inhibited by approximately 80% in alleles with 21 CA repeats. In experiments with polymerase chain reaction products that spanned a region of more than 4,000 base pairs and contained the promoter, two enhancers, and the polymorphic region in the first intron of the gene, we found that transcription activity declines with increasing numbers of CA dinucleotides. In vivo pre-mRNA expression data from cultured cell lines support these findings, although other regulation mechanisms can outweigh this effect. In addition, we showed that under our experimental conditions RNA elongation terminates at a site closely downstream of the simple sequence repeat and that there are two separate major transcription start sites. Our results provide new insights in individually different EGFR gene expression and the role of the CA repeat in transcription of this proto-oncogene.
Base Sequence↗
Chemosensitivity testing of oral cancer cells treated with a p185neu-specific agent.
The amplification and overexpression of the erbB-2 oncogene and its involvement in tumorigenesis makes this receptor an appropriate target for specific agents directed towards tumor cells. The purpose of this study was to evaluate the in vitro effect of the bacterially produced recombinant immunotoxin scFv(FRP5)-ETA on the protein synthesis and adenosine triphosphate (ATP) reduction in oral squamous cell carcinoma (OSCC) cells. This agent recognizes the erbB-2 receptor and inhibits protein synthesis in receptor-overexpressing cells. OSCC cells were selected for this study, and amplification and expression levels of the erbB-2 receptor were determined. Cell suspensions were cultured for 6 d with various concentrations of scFv(FRP5)-ETA (1-1000 ng/ml). A431 and MDA-MB468 cell lines were used as controls. Chemosensibility of tumor cells was measured by [3H]leucine incorporation assay and by an ATP luminescence assay. In OSCC cells with amplification and overexpression of erbB-2 inhibition, up to 92% of protein synthesis and 90% of ATP reduction was observed when cells were exposed to 1,000 ng/ml immunotoxin. In OSCC cells showing a deletion of erbB-2 and in erbB-2-negative MDA-MB468 cells, protein synthesis was inhibited by 22% and 8%, respectively. These results indicate that the effectiveness of a recombinant immunotoxin targeting erbB-2 receptors in OSCC cells depends on the level of erbB-2 amplification and expression, that it is highly specific for tumor cells expressing these receptors, and that a dose-dependency can be observed.
ADP Ribose Transferases↗
Aberrations of erbB-1 and erbB-2 oncogenes in non-dysplastic leukoplakias of the oral cavity.
The purpose of this study was to analyse erbB-1 and erbB-2 oncogenes in non-dysplastic oral leukoplakia to see if we could pinpoint the first steps towards dysplasia and possible carcinogenesis. Fresh biopsy specimens of leukoplakia in 13 patients with no history of oral cancer were examined using the competitive-differential polymerase chain reaction. The mean gene copy numbers of erbB-1 and erbB-2 were calculated from the formula to compare the absolute quantities of reference gene and oncogene from 24 patients who did not have leukoplakia. Healthy mucosa was taken as controls. In eight patients with leukoplakias, the results indicated aberrations of the erbB-1 oncogene, and two patients had gene dosage changes of erbB-2. There were no signs of deletions or amplifications in the controls. These results suggest that aberrations of erbB-1 and erbB-2 are additional markers in premalignant oral lesions at the beginning of the carcinogenic process, and that genetic alterations in histologically non-dysplastic premalignant oral lesions are common.
Adult↗
Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.
OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.
Aneuploidy↗
Reconstruction of the mitral and aortic annuli for advanced management of the Shone complex.
Shone's complex is a congenital cardiac abnormality which consists of surpravalvular mitral ring, parachute mitral valve, subaortic stenosis and aortic coarctation. Initial operative management has traditionally proven difficult, with multiple procedures often necessary to control symptoms. Advanced management had required a careful, individual approach based on both clinical and anatomic patient presentation. We present the first patient in whom mitral and aortic annular reconstruction with bovine pericardial gussets was successful in managing the late sequelae of Shone complex.
Adult↗
[Prostatic abscesses: what treatment to propose?].
Microscopic abscesses of the prostate (< 1 cm) are usually treated by antibiotics with good prostatic diffusion, such as fluoroquinolones, for a minimum of 4 to 6 weeks. Complementary surgical drainage is generally required for larger abscesses or in case of an unfavourable course. The main points of discussion in the literature are the type of drainage and the incision that should be performed. Prostatic abscesses used to be drained via perineal incisions, but with a high mortality. The use of effective antibiotics has significantly improved the morbidity of prostatic abscesses. CT-guided percutaneous drainage (perineal or transrectal), or more frequently transrectal ultrasound-guided drainage, now allows rapid and effective evacuation of the abscess, without the need for general anaesthesia. The perineal route allows a simple J stent to be left in place for several days to ensure complete drainage, but it is not universally accepted. Transurethral exposure is indicated for periurethral prostatic abscesses.
Abscess↗
Differential expression of alternatively spliced c-erbB-2 mRNA in primary tumors, lymph node metastases, and bone marrow micrometastases from breast cancer patients.
We established an RT-PCR method to measure the amount of a 2.3-kb alternatively spliced mRNA of the human c-erbB-2/HER-2 proto-oncogene relative to the 4.6-kb full-length transcript. For the first time, we demonstrated production of c-erbB-2 extracellular domains via alternative splicing in breast cancer tissues, lymph node and bone marrow micrometastases. In 15 c-erbB-2-positive primary breast tumor samples, we found two significantly distinct subgroups: 6/15 had a low level of the extracellular fragment, and 9/15 showed an average 4.4-fold higher amount of the alternatively spliced mRNA. Additionally, six lymph nodes and six bone marrow aspirates from metastatic breast cancer patients were analyzed: 5/6 lymph nodes and 6/6 bone marrow aspirates were found to produce elevated relative amounts of the truncated fragment. The results demonstrate that our method is suitable for sensitive detection of c-erbB-2-positive micrometastasis and strongly suggest that the alternatively spliced c-erbB-2 variant is involved in the development of micrometastasis in breast cancer.
Alternative Splicing↗