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C Behrens

Publications and source records attributed to C Behrens.

At least 37 records · Page 2Linked to original sources
PubMed1999

Molecular abnormalities associated with secretory carcinomas of the breast.

Secretory carcinomas (SCAs) represent a unique histological variant of invasive breast carcinomas, occurring predominantly in patients younger than 30 years of age. Data from limited series have shown SCAs to have a favorable prognosis in patients younger than 20 years of age, whereas the clinical course tends to parallel the more common in filtrating ductal carcinomas (IDCs) in patients older than 20 years. There are no reports on the molecular abnormalities associated with this unusual tumor. Microdissected archival formalin-fixed tissue from 10 SCAs collected from 2 institutions were used to determine the frequencies of allelic loss at 13 chromosomal regions with 19 microsatellite markers, using multiplex polymerase chain reaction (PCR)-based techniques. The results of loss of heterozygosity (LOH) and microsatellite alterations (MAs) analyses were compared with 20 cases of IDCs. P53 gene mutation analysis was also performed on the 10 SCAs using single-strand conformation polymorphism (SSCP) analysis, followed by sequencing of abnormal bands. LOH at multiple regions of chromosome 3p were the most common abnormality in both SCAs (55%) and IDCs (50%), followed by LOH at 17q21 (BRCA1 locus), 13q14 (retinoblastoma gene locus), and 8p21-23. No significant differences were seen in the frequencies of LOH at any chromosomal region except for 17p13 (p53 gene locus), where allelic losses were absent in SCAs, but evident in 46% of IDCs (P < .05). The 2 histological entities were similar in the fractional regional loss (FRL) index (0.26 v 0.24), fractional allelic loss (FAL) index (0.23 v 0.27), as well as in the frequency of MAs (0.015 v 0.005), P > .05. P53 gene missense mutation (G:C::A:T) was detected in 1 of 10(10%) SCAs. Based on the considerable similarities in the molecular abnormalities associated with both tumors, the formation of secondary lumina in both the in situ and the invasive components, as well as suggestions from limited series that the clinical behavior in adult patients parallels that of IDCs, SCA most likely reflects a secretory variant of IDCs.

Adult↗
PubMed1999

Pathogenesis of non-AIDS-defining cancers: a review.

As the AIDS epidemic advances, the number of HIV-infected subjects developing AIDS-related neoplasms is rapidly increasing, and the spectrum of malignancies encountered is expanding. Several non-AIDS-defining cancers are being reported at an increasing incidence in HIV-infected individuals, including anal, skin, oral mucosa, head and neck and lung carcinomas, testicular tumors, and pediatric soft-tissue sarcoma. There appears to be an emerging role for various concurrent viral infections in the HIV-infected host that are likely implicated in the pathogenesis of some nondefining-AIDS neoplasms. Our recent findings in HIV-associated lung cancers and in the precursor lesions of cervical carcinoma suggest that wide-spread genomic instability, as manifested by the development of increased numbers of microsatellite alterations (MAs), may occur frequently in HIV-associated tumors and they may play an important role in the pathogenesis of those neoplasms. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors. It will be important to track the epidemiological and biological features of non-AIDS-defining cancers in HIV-infected patients, and compare them to those tumors in the general population. It is likely that further clues about malignant transformation and oncogenesis unraveled in the HIV setting will have broad clinical implications.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Construction and characterization of murine neuroblastoma cell clones allowing inducible and high expression of the prion protein.

A tetracycline-inducible expression system has been established for the prion protein (PrP) in murine neuroblastoma cells (N2a). For this purpose, N2a cells were first stably transfected with either the tetracycline-controlled transactivator or the reverse transactivator. After selection of N2a clones which carried one of these transactivators, the murine PrP gene (Prnp) was introduced under the control of the transactivator-responsive promoter in a second round of stable transfection. Stably double-transfected N2a clones carrying the reverse type but not the normal transactivator were found to be fully inducible, giving a low background of Prnp expression before induction and high expression after induction. Stably double-transfected N2a cells were at least as productive as N2a cells over-expressing Prnp permanently under the control of a strong viral promoter. Furthermore, the selected N2a clones allowed the Prnp expression level to be quantitatively controlled by varying the level of the effector substance, the tetracycline-derivative doxycycline. The clones were fully controllable, as over-expression could be switched on and off as desired. These N2a clones may become an important tool for elucidation of the cellular function of PrP and may pave the way for the tetracycline-inducible expression of many genes in this neuroblastoma cell line.

Animals↗
PubMed1999

Comparison of features of human lung cancer cell lines and their corresponding tumors.

Although human lung tumor-derived cell lines play an important role in the investigation of lung cancer biology and genetics, there is no comprehensive study comparing the genotypic and phenotypic properties of lung cancer cell lines with those of the individual tumors from which they were derived. We compared a variety of properties of 12 human non-small cell lung carcinoma (NSCLC) cell lines (cultured for a median period of 39 months; range, 12-69) and their corresponding archival tumor tissues. There was, in general, an excellent concordance between the lung tumor cell lines and their corresponding tumor tissues for morphology (100%), the presence of aneuploidy (100%), immunohistochemical expression of HER2/neu (100%) and p53 proteins (100%), loss of heterozygosity at 13 chromosomal regions analyzed (97%) using 37 microsatellite markers, microsatellite alterations (MAs, 75%), TP53 (67%), and K-ras (100%) gene mutations. In addition, there was 100% concordance for the parental allele lost in all 115 comparisons of allelic losses. Some discrepancies were found; more aneuploid subpopulations of cells were detected in the cell lines as well as higher incidences of TP53 mutations (4 of 10 mutations not found in the tumors) and microsatellite alterations (two cell lines with MAs not detected in the tumors). Similar loss of heterozygosity frequencies by chromosomal regions and mean fractional allelic loss index were detected between successfully cultured and 40 uncultured lung tumors (0.45 and 0.49, respectively), indicating that both groups were similar. Our findings indicate that the NSCLC cell lines in the large majority of instances retain the properties of their parental tumors for lengthy culture periods. NSCLC cell lines appear very representative of the lung cancer tumor from which they were derived and thus provide suitable model systems for biomedical studies of this important neoplasm.

Adult↗
PubMed1998

Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects.

CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. OBJECTIVE: To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS: Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. SETTING: University-based medical centers and affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. RESULTS: The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS: Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.

Adult↗
PubMed1998

A combinatorial approach to new DNA minor groove binders.

A combinatorial approach towards new DNA minor groove binders capable of recognizing GC base pairs is reported. From a partly AT--biased library of 5832 different octapeptides of the type Py-Py-X1-X2-X3-Py-Py-gamma Abu synthesized following the one bead one compound methodology, two compounds containing the central peptide sequences Val-beta Ala-Tyr and Pip-beta Ala-Tyr were selected by a fluorescence--double stranded DNA probing assay using the sequence 5'-TTTGTTT-3' as the probe. The two hits were independently synthesized and binding to a recombinant pUC-19 EcoRl/Pvull DNA restriction fragment containing the sequence 5'-TTTGTTT-3' demonstrated. Binding constants to eight targets in the DNA fragment were estimated from quantitative DNAse I footprinting.

Amino Acid Sequence↗
PubMed1998

Comparison of features of human breast cancer cell lines and their corresponding tumors.

Although human tumor-derived cell lines play an important role in the investigation of cancer biology and genetics, there is no comprehensive study comparing tumor cell line properties with those of the individual tumors from which they were derived. We compared the properties of a series of 18 human breast cancer cell lines that were cultured for a median period of 25 months (range, 9-60 months) and their corresponding archival tumor tissues. We compared morphological characteristics, ploidy, and immunohistochemical expression of estrogen receptors, progesterone receptors, and HER2/neu and p53 proteins. For 17 of these cases, we also tested for allelic losses at 18 chromosomal regions frequently deleted in breast tumors using 51 polymorphic microsatellite markers, and we determined the TP53 gene mutation status in exons 5 to 10. There was an excellent correlation between the breast tumor cell lines and their corresponding tumor tissues for morphological features (100%); presence of aneuploidy (87%); immunohistochemical expression of estrogen receptors (87%), progesterone receptors (73%), and HER2/neu (93%) and p53 proteins (100%); allelic loss at all of the chromosomal regions analyzed (82-100% concordance); and TP53 gene mutations (75%). The same parental allele was lost in 279 (99%) of 281 of the comparisons of allelic losses. The fractional allelic loss indices (a reflection of the total allelic loss) of the cell lines and their corresponding tumor tissues were identical or similar in 15 (88%) of 17 paired comparisons. Although our previous studies (A. Gazdar et al., Int. J. Cancer, in press) indicated that only a subset of primary breast carcinomas that have several features indicative of advanced tumors with poor prognosis can be successfully cultured, the cell lines retain the properties of their parental tumors for lengthy culture periods and, thus, provide suitable model systems for biomedical studies.

Adult↗
PubMed1997

Molecular damage in the bronchial epithelium of current and former smokers.

BACKGROUND: Most lung cancers are attributed to smoking. These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions. In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers. METHODS: Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers. Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations). RESULTS: LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens. About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage. A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer. LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene). Microsatellite alterations were detected in 64% of the smokers. No genetic alterations were detected in nonsmokers. CONCLUSIONS: Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation.

Adult↗
PubMed1997

Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands.

The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast and other cancers. We investigated FHIT and FRA3B for loss of heterozygosity (LOH); homozygous deletions; abnormal transcripts; and acquired/germ-line point mutations in breast cancer cell lines (n = 32), breast epithelial and stromal cell cultures (n = 18), microdissected invasive (n = 16) and ductal in situ carcinomas (n = 6), and their accompanying normal and abnormal epithelial foci (n = 14). LOH at 3p14.2, especially at FHIT intragenic marker D3S1300, was found in 6 of 16 microdissected invasive tumors and 3 of 6 ductal in situ carcinomas. In accompanying preneoplastic foci, LOH occurred in two of eight intraductal hyperplasias but not in histologically normal ductal epithelium (n = 6). Three of 32 (9%) breast cancer cell lines demonstrated homozygous deletions of FHIT exon 4 (two cases) and exon 5 (one case), which correlated with exon 4-deleted transcripts and loss of the cDNA transcript containing the coding exons 5-9, respectively. Normal mammary cultures and 31 of 32 tumor cell lines (97%) expressed wild-type coding transcripts as well as a minor exon 8-deleted message. Single-strand conformation polymorphism analysis of the coding exons in the 32 tumor and 18 normal breast cell lines and their sequencing revealed four silent polymorphisms and a germ-line histidine triad point mutation (651 G-->T) in a tumor arising in a 70-year-old woman. This mutation was also present in one of her two thus far unaffected daughters. Analysis of additional DNAs from 280 probands of high-risk breast cancer families for other FHIT exon 8 mutations detected an intronic point mutation 13 bases upstream of exon 8. Thus, we have demonstrated relatively early abnormalities of the FHIT/FRA3B region in breast cancer and discovered two rare FHIT germ-line mutations. The expression of a transcript containing the coding exons in nearly all cell lines, including those with germ-line mutations, suggests the possibility that another gene in the FRA3B region may be involved in the pathogenesis of breast cancer.

Acid Anhydride Hydrolases↗
PubMed1997

Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma.

To study the molecular abnormalities involved in the multistage development of cervical carcinoma (CC), we investigated the presence of oncogenic human papillomavirus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite alterations at several genes/loci at 3p (3p14.2 at the FHIT gene, 3p14.3-21.1, 3p21, and 3p22-24.2), 9p21, RB and P53, and P53 gene point mutations in precisely microdissected archival tissues from 20 CCs and their accompanying precursor lesions (cervical intraepithelial neoplasia, CIN; n = 40) and normal epithelia (n = 20). In all HPV-positive cases (90% of CCs), HPV sequences were detected as the earliest appearing molecular change or simultaneously with other changes. LOH at any 3p region was found in 70% of CCs, and 3p14.2 (FHIT gene/FRA3B fragile site) (56%) and 3p21 (57%) were the most frequent 3p sites of loss. LOH at some 3p region was in the CIN I stage, and the 3p deletions in precursor CIN lesions were smaller than the 3p losses found in the associated invasive CC. LOH at the other regions studied and P53 gene mutations were less frequent and later events. Microsatellite alterations were detected in 35% of CCs, and identical abnormalities were detected in the associated precursor lesions. Although infection with oncogenic HPV strains is the earliest and most frequent molecular event, progressive deletions at one or more 3p regions (particularly at 3p14.2, and 3p21) are also frequent events occurring early in the pathogenesis of CC.

Acid Anhydride Hydrolases↗
PubMed1997

Remote memory in patients with acute brain injuries.

Remote memory was investigated in an unselected sample of 26 patients with either unilateral tumours in the temporal lobes or traumatic brain injuries. Six patients underwent excisions within the left temporal lobe, and nine patients were operated on within the right temporal lobe. In both groups, patients with excisions including and sparing the hippocampal formation were studied. Their performance was compared to that of 11 patients with moderate to severe head trauma and to a normative sample of 214 healthy controls. Remote memory was assessed using a famous events test with items of extremely low salience that had been proven to be of low difficulty for those old enough at the time of the event's actuality. The results show severely disturbed retrograde memory functions in the left temporal tumour group. These patients achieved similar scores to patients with severe traumatic brain injury. Right hemispheric patients showed a pattern of results comparable to that of healthy controls. The strongest effects were in the free recall part of the test. In most of the patients, no graded memory loss was observable. No consistent association to recent memory function could be identified. Since most of the remote memory test items used denoted famous names which were cued by rich semantic information, the type of deficit seen may be best understood in terms of a specific dysfunction of the semantic stores containing information about famous proper names.

Adult↗
PubMed1997

External four channel tocography in preterm labor. First results.

In order to known more about preterm labor the objective of our investigation was to look for a correlation between the spatial and temporal pattern of uterine contractions and the duration of pregnancy. 50 patients with preterm labor between 21 and 35 weeks of gestation underwent repeated measurements using four-channel tocography in which the pressure of contractions was registered simultaneously on the left and right sides at the fundus and the lower segment of the uterus. Half of all recorded signals were locally restricted (typical labor pattern in only one or two registration tracks). The following two phenomena were significantly associated with a shorter duration of pregnancy: 1. the reproducibility of a center of dominance (defined as the locus of registration with the highest sum of amplitudes), and 2. a predominant origin of labor in the right fundal region of the uterus. Four-channel tocography indicates whether preterm labor is likely to lead to preterm delivery. It may therefore help the obstetrician in deciding whether to use tocolytic therapy.

Adolescent↗
PubMed1993

PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules.

DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes, and bind to double-stranded DNA by strand displacement. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.

Base Sequence↗
PubMed1993

Inhibition of gonadotrophin release in mares during the luteal phase of the oestrous cycle by endogenous opioids.

Effects of the opioid antagonist naloxone on concentrations of LH and FSH in plasma were measured in mares during different stages of the oestrous cycle. During the follicular phase of the cycle, naloxone (300 mg i.v.) had no discernible effects on basal concentrations of LH and FSH. A significant increase in plasma LH (P < 0.01) and FSH (P < 0.05) concentrations was observed after naloxone in mares during the luteal phase. This response was not different between suckled and non-suckled mares. The gonadotrophin-releasing hormone analogue buserelin (0.02 mg i.v.) caused a significant (P < 0.05) LH and FSH release irrespective of the stage of the oestrous cycle and a previous naloxone treatment. The results of this study indicate that endogenous opioid peptides are involved in the inhibition of LH and FSH release during the luteal phase of the oestrous cycle in mares and may partially mediate the suppressive influence of progesterone on gonadotrophin secretion. The opioid-mediated suppression of LH and FSH release does not seem to be affected by suckling.

Animals↗
PubMed1993

[Prevalence of hepatitis C virus antibodies in chronic hemodialysis and kidney transplantation patients].

Hepatitis C virus antibodies were measured in 26 chronic hemodialyzed patients and 43 kidney transplant recipients, using a second generation ELISA method. Fifty four percent of hemodialyzed had a longer duration of dialysis treatment compared with patients with negative antibodies (57.6 +/- 30.5 vs 15.4 +/- 7.3 months), and did not differ in the number of transfusions. Seven patients had elevated serum transaminase values, all with positive antibodies. Thirty five percent of kidney transplant recipients had positive antibodies. In these subjects, no relation was observed between the number of transfusions or length of dialysis treatment and the presence of positive hepatitis C antibodies.

Adult↗
PubMed1993

[An unusual combination of different organ and skeletal abnormalities in a black and white calf].

This is a case report of a rare malformation in a calf: duplicitas posterior incompleta in combination with multiple malformations (diphallia, polymelia, polydactylism, lack of the bony floor of the pelvis, asymmetrical pelvis, asymmetrical sacral and coccygeal vertebrae, unilateral hypoplasia of the kidneys). A detailed description of the clinical and pathological findings is presented.

Abnormalities, Multiple↗
PubMed1990

[Continuous intrathecal baclofen therapy using an implantable pump system in severe spasticity].

Spasticity is an expression of a damage of the motor neurone associated with velocity dependent increase of the muscle tone. Since 1986 21 patients with severe spasticity mainly in multiple sclerosis were treated with an implantable pump system to administrate continuously Baclofen intrathecally. Even with a very small dosage of Baclofen patients who were previously treated until intoxication without success there was a favorable reduction in spasticity. Therefore we propose to perform this procedure before using surgical methods or stimulating methods.

Baclofen↗