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Biomedical subjects

H Skovgaard Poulsen

Publications and source records attributed to H Skovgaard Poulsen.

11 recordsLinked to original sources

Cellular telephones and risk for brain tumors: a population-based, incident case-control study.

OBJECTIVE: To evaluate a possible association of glioma or meningioma with use of cellular telephones, using a nationwide population-based case-control study of incident cases of meningioma and glioma. METHODS: The authors ascertained all incident cases of glioma and meningioma diagnosed in Denmark between September 1, 2000, and August 31, 2002. They enrolled 252 persons with glioma and 175 persons with meningioma aged 20 to 69. The authors also enrolled 822 randomly sampled, population-based controls matched for age and sex. Information was obtained from personal interviews, medical records containing diagnoses, and the results of radiologic examinations. For a small number of cases and controls, the authors obtained the numbers of incoming and outgoing calls. They evaluated the memory of the respondents with the Mini-Mental State Examination and obtained data on socioeconomic factors from Statistics Denmark. RESULTS: There were no material socioeconomic differences between cases and controls or participants and non-participants. Use of cellular telephone was associated with a low risk for high-grade glioma (OR, 0.58; 95% CI, 0.37 to 0.90). The risk estimates were closer to unity for low-grade glioma (1.08; 0.58 to 2.00) and meningioma (1.00; 0.54 to 1.28). CONCLUSION: The results do not support an association between use of cellular telephones and risk for glioma or meningioma.

Adult↗

Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines.

Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines. Northern blot analysis showed that RII RNA expression was very weak in 16 of 21 cell lines. To investigate if the absence of RII transcript was due to mutations, we screened the poly-A tract for mutations, but no mutations were detected. Additional screening for mutations of the RII gene revealed a GG to TT base substitution in one cell line, which did not express RII. This mutation generates a stop codon resulting in predicted synthesis of a truncated RII of 219 amino acids. The nature of the mutation, which has not previously been observed in RII, has been linked to exposure to benzo[a]-pyrene, a component of cigarette smoke. Since RII has been mapped to chromosome 3p22 and nearby loci are often hypermethylated in SCLC, it was examined whether the lack of RII expression was due to hypermethylation. Southern blot analysis of the RII promoter did not show altered methylation patterns. The restriction endonuclease pattern of the RII gene was altered in two SCLC cell lines when digested with Smal. However, treatment with 5-aza-2'-deoxycytidine did not induce expression of RII mRNA. Our results indicate that in SCLC lack of RII mRNA is not commonly due to mutations and inactivation of RII transcription was not due to hypermethylation of the RII promoter or gene. Thus, these data show that in most cases of the SCLC cell lines, the RII gene and promoter is intact in spite of absent RII expression. However, the nature of the mutation found could suggest that it was caused by cigarette smoking.

Blotting, Northern↗

In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor.

Formation of metastasis is a multistep process involving attachment to the basement membrane, local proteolysis and migration into surrounding tissues, lymph or bloodstream. In the present study, we have analysed the correlation between in vitro invasion and presence of the epidermal growth factor receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16% of the cells added to the upper chamber were able to traverse the Matrigel membrane. Expression of several matrix metalloproteases (MMP), of tissue inhibitor of MMP (TIMP) and of cathepsin B was evaluated by immunoprecipitation, Western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition of this antibody resulted in a significant reduction of the in vitro invasion in three selected EGFR-positive cell lines. Our results show that only EGFR-positive SCLC cell lines had the in vitro invasive phenotype, and it is therefore suggested that the EGFR might play an important role for the invasion potential of SCLC cell lines.

Antibodies, Monoclonal↗

Growth suppression by transforming growth factor beta 1 of human small-cell lung cancer cell lines is associated with expression of the type II receptor.

Nine human small-cell lung cancer cell lines were treated with transforming growth factor beta 1 (TGF-beta 1). Seven of the cell lines expressed receptors for transforming growth factor beta (TGF-beta-r) in different combinations between the three human subtypes I, II and III, and two were receptor negative. Growth suppression was induced by TGF-beta 1 exclusively in the five cell lines expressing the type II receptor. For the first time growth suppression by TGF-beta 1 of a cell line expressing the type II receptor without coexpression of the type I receptor is reported. No effect on growth was observed in two cell lines expressing only type III receptor and in TGF-beta-r negative cell lines. In two cell lines expressing all three receptor types, growth suppression was accompanied by morphological changes. To evaluate the possible involvement of the retinoblastoma protein (pRb) in mediating the growth-suppressive effect of TGF-beta 1, the expression of functional pRb, as characterised by nuclear localisation, was examined by immunocytochemistry. Nuclear association of pRb was only seen in two of the five TGF-beta 1-responsive cell lines. These results indicate that in SCLC pRb is not required for mediation of TGF-beta 1-induced growth suppression.

Carcinoma, Small Cell↗

Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines.

A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell lines express TGF beta-receptors and also produce TGF beta mRNAs.

Blotting, Northern↗

[Bone metastasis].

Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumour originates from the breast, prostate or lungs. Even although the prognosis is serious, a proportion of the patients will survive for several years and will thus require active treatment. More than 25% of the patients have no symptoms whereas pain dominates in the remainder. Frequent complications are pathological fractures, hypercalcaemia and spinal cord compression. Normally, the diagnosis can be established from the clinical picture compared with a series of laboratory analyses, x-ray investigations of the skeleton and bone scintigraphy. As treatment is mainly palliative, the purpose is primarily relief of pain, prevention of fractures and ensuring a reasonable functional level. The therapeutic possibilities comprise local treatment in the form of surgery and irradiation and also systemic treatment in the form of chemotherapy, endocrine therapy and possibly diphosphonates. of these, irradiation still plays the most important role. About 80% of the patients respond to treatment and, after 12 months, 50-70% of the surviving patients will still be free from pain. Only few randomized investigations are found in the literature available and the criteria of response are, in general, difficult to interpret. There is, therefore, a great requirement for more clinically controlled investigations which assess the efficacy of the numerous therapeutic possibilities.

Bone Neoplasms↗

Diagnostic reliability of combined physical examination, mammography, and fine-needle puncture ("triple-test") in breast tumors. A prospective study.

A prospective study of 622 consecutively registered patients with 650 breast tumors was performed to appraise the reliability of combined physical examination, mammography, and fine-needle puncture (triple test) in the preoperative diagnosis of such tumors. All malignant as well as benign test results were confirmed by subsequent histologic examination. The diagnostic accuracy of the triple test at benign changes is comparable to that of histologic examination, but participation of experienced radiologists and cytologists as well as persons skilled in fine-needle puncture is required. Twenty-eight percent of the planned excisional biopsies were made superfluous by the fine-needle puncture, which immediately revealed the tumor as a cyst, abscess, or hematoma. For this reason, too, fine-needle puncture is recommended as a routine procedure.

Biopsy, Needle↗

Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice.

A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth curves, and by the changes in the cell cycle distribution monitored by flow cytometric DNA analysis. The results demonstrated that both oestradiol and tamoxifen induced a temporary growth delay, whereas ovariectomy of the host had no effect on the growth of the tumour. The oestradiol-induced tumour growth delay was accompanied by a decrease in the G1 fraction, an accumulation of cells in the S-phase, and polyploidy, whereas neither treatment with tamoxifen nor ovariectomy influenced cell cycle distribution. The results indicate that oestradiol and tamoxifen have different mechanisms of action. In addition, they were interpreted as indicating different mechanisms regulating ovarian-dependent tumour growth, on the one hand, and oestrogen and tamoxifen-induced tumour growth inhibition, on the other. The results support the view that the presence of receptors may be of importance but is not a sufficiently clear marker to allow prediction of the endocrine sensitivity of individual breast tumours.

Animals↗

Palpable breast tumours: "triple diagnosis" and operative strategy. Results of a prospective study.

A prospective study of 292 consecutive patients with 303 tumours was performed to appraise the combination of physical examination, mammography and fine-needle puncture (triple test) in the diagnosis of breast tumours. The diagnostic accuracy of the triple test was 100%. Because of its relative smallness, however, the series does not permit the conclusion that a benign result of triple test makes excisional biopsy unnecessary. It is emphasized that a follow-up regimen with participation of radiologists and cytologists is required. Fine-needle puncture with cytologic examination of the aspirate is recommended as a routine procedure in the diagnosis of breast tumours.

Biopsy, Needle↗