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M Hillemanns

Publications and source records attributed to M Hillemanns.

8 recordsLinked to original sources
PubMed2004

Inducible nonviral gene expression in the treatment of osteochondral defects.

OBJECTIVE: The repair of osteochondral defects with chondrocytes genetically modified to express desired growth factors promises great potential in orthopaedic therapy. Controlled expression of the transgenes is required in many instances. The objective of the present study was to demonstrate the inducibility of tetracycline-responsive transgene expression in osteochondral defects in the knee joint filled with genetically modified chondrocyte implants. METHODS: An expression plasmid containing the lacZ gene under the control of the minimal CMV promoter fused to the Tet-responsible element (TRE) as well as the reverse transactivator (rtTA2s-M2) was constructed and used to transfect isolated articular chondrocytes from New Zealand white rabbits. rtTA2s-M2 binds to the TRE in the presence of tetracycline and leads to the transcription of the transgene. Different concentrations of DNA and various DNA:lipid ratios were tested to determine best transfection conditions. Transfection efficiency and inducibility were analysed by histochemical analysis and flow-cytometry. To evaluate the system in vivo, collagen-sponges were seeded with transfected autologous chondrocytes and implanted in osteochondral defects in the knees of NZW-rabbits. Gene expression was induced by doxycycline and 3 weeks later, LacZ-expression in isolated knee joints was evaluated in histological sections by X-gal staining. RESULTS: In vitro 13.5% (+/-1.32) of induced primary chondrocytes were LacZ-positive, while non-induced controls showed a background-staining in 0.6% (+/-0.2). In vivo, upon doxycycline treatment, induction of lacZ-gene-expression could be demonstrated in chondrocytes in 3-week-old, well-integrated implants. CONCLUSION: For the first time, tetracycline-inducible gene expression is demonstrated to work in the treatment of osteochondral defects. This demonstrates the feasibility for a gene therapy-assisted approach using controlled expression of therapeutic growth factors from transplanted genetically modified chondrocytes.

3T3 Cells↗
PubMed2001

Giant malignant mesenchymoma of the spermatic cord with bidirectional differentiation.

BACKGROUND: Spermatic cord neoplasms are a rare tumor entity and, moreover, of benign behavior. Malignant tumors of the spermatic cord are mostly of mesenchymal origin. We present the unusual case of a giant malignant mesenchymoma of the spermatic cord with bidirectional differentiation into a liposarcoma and a leiomyosarcoma. CASE REPORT: A 84-year-old male patient presented with a scrotal mass on the left side which was observed growing since 1 year and misdiagnosed as scrotal hernia or testicular hydrocele. Ultrasound and computed tomography demonstrated a solid tumor suggesting a spermatic cord tumor. The patient underwent hemiscrotectomy, and the histological examination of the 2,500-gram specimen revealed a malignant mesenchymoma originating from the spermatic cord with two distinct histopathological compartments of liposarcoma and leiomyosarcoma. Because an adjuvant therapy protocol is of questionable effect and because of the patient's age no further therapy was applied. The patient was closely followed and is now, 5 years after surgery, still free of disease. CONCLUSION: Even in older patients, scrotal masses should be considered malignant tumors as long as no benign diagnosis has been proven. Although malignant mesenchymomas are rare tumors with poor prognosis, in selected cases even large tumor masses, as presented, can be cured by surgery.

Aged↗
PubMed2000

[Current classification of gastrointestinal stromal tumors].

Gastrointestinal mesenchymal tumors traditionally have been designated as smooth muscle tumors. However, with increasingly accurate analytic tools most investigators were unable to demonstrate true myogenic differentiation. Diagnostic criteria and grading vary among different studies and the biological behavior of these gastrointestinal stromal tumors (GIST) is difficult to predict. In this manuscript the recent concept of GIST is reviewed, including a suggestion for tumor classification. Furthermore, MIB-1 and p53 immunohistochemistry and myogenic differentiation were evaluated as potential prognostic factors. Diagnosis requires the use of immunohistochemistry. Classification as GIST seems appropriate, since only few tumors show complete myogenic differentiation. Besides a tumor size over 5 cm, mitotic rate still seems to be the best predictor of treatment failure in tumors that are resected with a rim of uninvolved tissue. MIB-1 proliferation index above 4% and p53 positivity indicate a more aggressive course.

Antigens, Nuclear↗
PubMed1999

Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid.

OBJECTIVE: To evaluate the therapeutic effect of photodynamic therapy on vulvar lichen sclerosus. METHODS: Twelve women with lichen sclerosus were enrolled in a prospective, single-arm pilot study. Four to 5 hours before photodynamic therapy, 10 mL of a 20% solution of 5-aminolevulinic acid was applied topically to the vulva. Photodynamic therapy was administered with an irradiation of 80 J/cm2 at an irradiance of 40-70 mW/cm2. Light with a wavelength of 635 nm was delivered by an argon ion-pumped dye laser. The degree of pruritus was evaluated using a horizontal visual analog scale before and after 6-8 weeks, and patients were followed tri-monthly after photodynamic therapy. RESULTS: Two women underwent two cycles of photodynamic therapy, one underwent three cycles, and the remaining nine women underwent one cycle each. Treatment was tolerated moderately well, with eight patients not requiring any analgesia; three treated with opioids intravenously during the procedure, due to burning sensations; and one undergoing separation of adhesions under general anesthesia. Minimal local toxicity included vulvar erythema but no necrosis, sloughing, or scarring. No generalized cutaneous photosensitivity was present. Six to 8 weeks after photodynamic therapy, pruritus significantly improved in ten of the 12 women. A prolonged effect of photodynamic therapy was reported, with a mean of 6.1 months. CONCLUSION: Photodynamic therapy after topical application of 5-aminolevulinic acid produced statistically significant relief of symptoms of vulvar lichen sclerosus for an average of 6.1 months with minimal side effects.

Adult↗
PubMed1998

[Prognostic factors of gastrointestinal stromal tumors of the stomach].

The stomach is the most common gastrointestinal site of mesenchymal tumors which traditionally have been designated as smooth muscle tumors. However, with increasing analytic tools most investigators were unable to demonstrate true myogenic differentiation. Furthermore, the biological behavior of gastrointestinal stromal tumors (GIST) is difficult to predict. The aim of this study was to evaluate MIB-1 and p53 as additional prognostic markers, as well as myogenic differentiation immunohistochemically in GIST. 43 gastric stromal tumors were reviewed, 19 were classified as benign, and 10 as malignant. 14 tumors were considered indeterminate for biological behavior. In addition to MIB-1 and p53, immunohistochemistry was also performed for sm-actin, desmin and S 100-protein (ABC). 41 patients had a clinical follow-up of more than 2.5 years, 5 patients had metastases. Mean proliferation rates defined as percentage of MIB-1 positive tumor cells in 3 HPF were as follows: typical leiomyoma: 0.2%; benign GIST, spindle cell type: 1.8%; benign GIST, epithelioid cell type: 2.4%; borderline GIST, spindle cell type: 2.1%; borderline GIST, epithelioid cell type: 2.5%; malignant GIST, spindle cell type: 4.9%; and malignant GIST, epithelioid cell type: 7.3%. All 5 metastasizing tumors had a proliferation index > 4% (p < 0.0001). 4/5 metastasizing tumors had p53 positive cells (p < 0.05). 36/43 tumors were sm-actin positive, 7 of which were positive for desmin as well. Classification of gastric mesenchymal tumors as GIST is appropriate because only a small percentage show true smooth muscle differentiation. A MIB-1 proliferation index above 4% might indicate a more aggressive course, as well as p53 positivity.

Biomarkers, Tumor↗
PubMed1997

Botryoid-type embryonal rhabdomyosarcoma of liver in a young cat.

An unusual malignant mesenchymal tumor arising in the liver of a 2-year-old cat is described. Histologically, the tumor showed considerable variation in growth pattern, cellularity, and cell types. Phenotypical diversity was confirmed by immunohistochemistry, showing expression of desmin, vimentin, S-100, and neuron-specific enolase in various areas of the tumor. On the basis of histopathology, immunohistochemistry, electron microscopy, and gross morphology, the tumor was classified as botryoid-type embryonal rhabdomyosarcoma. Differential diagnosis included so-called undifferentiated (embryonal) sarcoma of the liver, a rare tumor of the pediatric age group in humans. Problems of tumor heterogeneity and differentiation in mesenchymal tumors are discussed.

Animals↗
PubMed1996

The diagnostic potential of the chromosome translocation t(2;13) in rhabdomyosarcoma: a Pcr study of fresh-frozen and paraffin-embedded tumour samples.

The chromosomal translocation t(2;13)(q35;q14) has been reported in alveolar paediatric rhabdomyosarcoma. The rearrangement leads to the juxtaposition of the PAX-3 and FORKHEAD genes and the production of a fusion protein with putative transcriptional regulatory activity. The diagnostic potential of this translocation has been examined using a reverse transcription polymerase chain reaction (RT-PCR) assay to detect translocations in both fresh-frozen and archival formalin-fixed, paraffin-embedded rhabdomyosarcoma. A total of 25 tumours and one cell line were examined. PAX-3-FORKHEAD chimeric mRNAs were amplified by PCR in 8 of 15 cases of alveolar rhabdomyosarcoma. Translocations were detectable in both fresh-frozen tissues (4 of 7) and paraffin-embedded tumours (3 of 7) and in the alveolar rhabdomyosarcoma cell line. Our study confirms that the t(2;13) translocation is not present in embryonal rhabdomyosarcomas, but can be detected in nearly half of alveolar rhabdomyosarcomas, whether fresh-frozen or paraffin-embedded. The PCR-based t(2;13) translocation assay can aid in the diagnosis of rhabdomyosarcoma, but cannot replace a careful histopathological evaluation. It may contribute in further characterizing an otherwise undifferentiated small cell tumour, where it may be indicative of clinical behaviour.

Blotting, Southern↗