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Biomedical subjects

Stefan Schultze-Mosgau

Publications and source records attributed to Stefan Schultze-Mosgau.

At least 19 recordsLinked to original sources

Plasminogen activator inhibitor-I-related regulation of procollagen I (alpha1 and alpha2) by antitransforming growth factor-beta1 treatment during radiation-impaired wound healing.

PURPOSE: Plasminogen activator inhibitor (PAI)-1 mediates transforming growth factor-beta1 (TGF-beta1)-related signaling by stimulating collagen Type I synthesis in radiation-impaired wound healing. The regulation of alpha(I)-procollagen is contradictory in fibroblasts of different fibrotic lesions. It is not known whether anti-TGF-beta1 treatment specifically inhibits alpha(I)-procollagen synthesis. We used an experimental wound healing study to address anti-TGF-beta1-associated influence on alpha(I)-procollagen synthesis. METHODS AND MATERIALS: A free flap was transplanted into the preirradiated (40 Gy) or nonirradiated neck region of Wistar rats: Group 1 (n = 8) surgery alone; Group 2 (n = 14) irradiation and surgery; Group 3 (n = 8) irradiation and surgery and anti-TGF-beta1 treatment. On the 14th postoperative day, skin samples were processed for fibroblast culture, in situ hybridization for TGF-beta1, immunohistochemistry, and immunoblotting for PAI-1, alpha1/alpha2(I)-procollagen. RESULTS: Anti-TGF-beta1 significantly reduced TGF-beta1 mRNA (p < 0.05) and PAI-1 expression (p < 0.05). Anti-TGF-beta1 treatment in vivo significantly reduced alpha1(I)-procollagen protein (p < 0.05) and the number of expressing cells (p < 0.05) in contrast to significantly increased (p < 0.05) alpha2(I)-procollagen expression. CONCLUSION: These results emphasize anti-TGF-beta1 treatment to reduce radiation-induced fibrosis by decreasing alpha1(I)-procollagen synthesis in vivo. alpha1(I)-procollagen and alpha2(I)-procollagen might be differentially regulated by anti-TGF-beta1 treatment. Increased TGF-beta signaling in irradiated skin fibroblasts seemed to be reversible, as shown by a reduction in PAI-1 expression after anti-TGF-beta1 treatment.

Animals↗

Neurophysiologic and long-term effects of clinical hypnosis in oral and maxillofacial treatment--a comparative interdisciplinary clinical study.

This prospective comparative clinical study evaluated the effectiveness of clinical hypnosis and its long-term effect in oral and maxillofacial treatment. A total of 45 highly anxious and nonanxious subjects were evaluated by subjective experience and objective parameters. Parameters were EEG, ECG, heart rate, blood pressure, blood oxygen saturation, respiration rate, salivary cortisol concentration, and body temperature. During and subsequent to the operative treatment, hypnosis led to a significant reduction of systolic blood pressure, and respiration rate and to significant changes in the EEG. The subjective values of the parameters evaluated existing anxiety mechanisms and patterns and possible strategies to control them, whereas the objective parameters proved the effectiveness of hypnosis and its long-term effect.

Anxiety↗

Increased metabolic activity of fibroblasts derived from cords compared with nodule fibroblasts sampling from patients with Dupuytren's contracture.

BACKGROUND: The pathogenesis of Dupuytren's contracture is characterized by progress in several stages. The disease process includes two structurally distinct fibrotic elements, the so-called nodule and the cord. Several hypotheses have been proposed regarding the cause. Until now, there has been ongoing discussion regarding whether cords or nodules are the primary source of the disease. METHODS: Tissues from 24 patients with Dupuytren's disease were obtained during hand surgery, providing samples from nodules and cords for cell culture. Tissue from the flexor retinaculum excised from healthy patients during surgical procedures on the hand served as control. By using the explant culture technique, fibroblasts were isolated and grown in standard medium. Besides morphological analysis, XTT proliferation tests were performed at various time periods to measure the metabolic activity of the cultivated fibroblasts. RESULTS: Statistical analysis revealed significant differences of nodule- and cord-derived fibroblasts after 1 hour (p = 0.0150), 8 hours (p < 0.0001), and 16 hours (p < 0.0001). CONCLUSIONS: The authors suggest that distinct proliferative properties of Dupuytren-derived fibroblasts are dependent on the cells' origin. Conclusions about the cause or pathogenesis cannot yet be drawn. Further investigation concerning their apparently different fibroproliferative properties is necessary.

Cells, Cultured↗

Interdisciplinary treatment and ophthalmological findings in Parry-Romberg syndrome.

Parry-Romberg syndrome is a rare pathologic process, characterized by progressive hemifacial atrophy. A case of Parry-Romberg syndrome with ocular involvement is reported. A 27-year-old male patient with Parry-Romberg syndrome was interdisciplinary investigated and treated. For reconstruction of hemifacial soft tissues a free vascular parascapular graft was performed. Opthalmological findings included an evident enophthalmos and an eyelid lag with keratopathy and epiphora. Furthermore pupillary disturbances and endothelial precipitates were detectable. Complete fundus examination showed a unilateral optic disc swelling, central vitreous opacities and peripheral pigmentary disturbances. In the presented case of Parry-Romberg syndrome a rare association to ophthalmological involvement could be found. Beside the enophthalmos and eyelid alterations, also a panuveitis with papillitis should be treated by steroid therapy.

Adult↗

Changes of mineralization of free autogenous bone grafts used for sinus floor elevation.

For augmentations before implant placement in areas of minor bone quantity, autogenous bone is considered the reference to all bone substitutes used alternatively. Autogenous bone transplants originate from various donor areas and can be prepared in different ways before augmentation. They may either be used as block grafts or may be milled to granules that can be used solitarily or in combination with a bone substitute. In a prospective study, 61 patients of the Maxillofacial Surgery Department of our University receiving two-stage sinus floor elevation because of insufficient bone supply were randomly selected. At first-stage surgery, the local augmentation procedure, monocortical probes were obtained on the site of bone harvesting. At second-stage surgery, the implant insertion 6 months after the elevation procedure, bone cores were harvested in the areas of implant placement. Donor regions were the following three areas: the posterior (N=28) and anterior pelvic region (N=15) and the chin region (N=18). The implanted bone in all three groups was particulated to granules of 2-3 mm(2) using a bone mill. All biopsies were analyzed by means of microradiography. The anterior pelvic bone grafts showed a mineralized tissue grade of 35.1+/-7.6% before milling and augmentation. The posterior pelvic bone grafts exhibited a mineralization of 30.7+/-9.5% and the chin bone grafts 74.6+/-8.6%. At second-stage surgery after 6 months, the mineralization was 36.1+/-7.59% in the areas where bone grafts from the anterior pelvic crest were used. Probes harvested from sites with posterior pelvic bone augmentations showed a mineralization rate of 34.5+/-6.5%, and sites were chin bone grafts were applied expressed a mineralization of 54+/-8.6% (P=0.003 compared with the pre-operative value). The comparison of the microradiographical results demonstrated significant differences in the mineralization grades depending on the origin of the graft. The origin of the grafts and their remodeling influenced the mineralization rates found at 6 months. How these data may influence the long-term clinical outcome considering implant survival and bone resorption has to be examined in further long-term studies.

Bone Density↗

PRP modulates expression of bone matrix proteins in vivo without long-term effects on bone formation.

This experimental study (domestic pig) examined the bone formation after filling defined defects of the frontal skull with autogenous bone or a deproteinized bovine bone matrix (DBBM) in combination with platelet-rich plasma (PRP). Six groups, both materials with and without PRP in two different concentrations (4.1x and 6.5x referring to untreated whole blood) were evaluated at 2, 4, 12, and 26 weeks by means of immunohistochemical staining for different bone matrix proteins, microradiography, light microscopy and polychromatic fluorescence labeling. The sequential expression of bone matrix proteins reflected the specific roles these proteins fulfil in the mineralization of hard tissue. Collagen I expression at 2 weeks was enhanced in all autogenous bone groups. No specific modification of the collagen I expression was found after use of DBBM with or without PRP. Osteopontin and especially osteonectin showed a remarkable enhancement at 4 weeks in nearly all autogenous bone and DBBM groups. These increased levels closely resembled the mineralization content evaluated by microradiography at that time. For the three autogenous bone groups, an expression peak for osteocalcin was demonstrated at 12 weeks, further reflecting the way of de novo bone formation. The microradiographic evaluation demonstrated a statistically significant enhancement in bone regeneration by PRP only after use of autogenous bone plus PRP at 2 weeks (P = 0.002). After 4 weeks, mineralization values after use of autogenous bone were significantly lower if PRP was added to the autogenous bone (P = 0.002). No long-term effects of the PRP administration were found in the mineralization process. In all DBBM groups, bone formation remained unchanged, confirming the lack of any osteoinductive capacity of PRP. PRP modulated the expression of bone matrix proteins in this experimental setting. However, an enhancement of bone formation was demonstrated only at 2 weeks after application of the higher PRP concentration in combination with autogenous bone. In conjunction with an anorganic bovine bone no effects of PRP on defect mineralization were discovered, demonstrating the lack of osteoinductive capacity in PRP as well as in DBBM.

Animals↗

Acceleration of de novo bone formation following application of autogenous bone to particulated anorganic bovine material in vivo.

OBJECTIVE: This prospective animal study examined the de novo bone formation following application of deproteinized bovine bone matrix (DBBM) with or without autogenous bone (AB) to osseous defects. STUDY DESIGN: Defects of defined size were created in the frontal skull of domestic pigs and filled with DBBM alone (group A) and DBBM+25%AB (group B). De novo bone formation was analyzed qualitatively and quantitatively at 9 different times (0.5, 1, 2, 3, 4, 6, 8, 12, 26 weeks) by means of light microscopy, microradiography, and statistical analysis. RESULTS: Histological analysis indicated sufficient osseointegration of DBBM in both groups. Microradiography demonstrated a significant increase of bone formation in group B after 6 weeks (P = .0159) and 8 weeks (P = .0317). CONCLUSION: The addition of 25%AB to DBBM results in accelerated de novo bone formation in osseous defects. This effect is likely caused by osteoinductive properties of cellular elements transplanted with the autogenous bone.

Animals↗

Bioactivation of an anorganic bone matrix by P-15 peptide for the promotion of early bone formation.

This animal experiment compared the regenerative processes within defined bony defects of the porcine skull after delivery of routinely utilized bone graft materials: anorganic bone matrix (ABM) and an identical ABM carrying the cell binding peptide P-15. Particulated autogenous bone was used as a control group. The chosen porcine model guaranteed the transferability of the obtained results to clinical practice. A total observation period of 6 months was defined. The bone samples were examined microradiographically and histologically at 8 specific times. Sufficient osseointegration and osseoconduction could be demonstrated for both anorganic bone minerals. However, in the selected model significantly higher mineralization rates (p = 0.0286) were found in the microradiographic image at 12 weeks after application of the bioactive form. The histological examination confirmed this accelerating effect on bone formation starting at day 3. At the end of the study after 6 months, the mineralization values had equalized in both study groups. For the first time, the material was demonstrated to be suitable as a bone substitute material for the treatment of larger bony defects in a large animal model. The P-15 sequence accelerated the process of bone formation on the surface of the anorganic bone matrix as early as 3 days but was not traced over the whole term of the study.

Animals↗

Enhanced bone regeneration with a synthetic cell-binding peptide--in vivo results.

This in vivo study compared the regenerative processes within defined defects of the porcine skull after delivery of a porous algae-derived hydroxyapatite (adHA), a similar, experimental adHA carrying the cell binding peptide P-15, used solely and in combination with 25% autogenous bone (AB). Particulated AB served as a control group. During an observation period of 26 weeks, microradiography and histology were performed at four specific times. Significantly higher mineralization rates (p=0.008) were found 4 weeks after application of the bioactive material in combination with AB. At 12 weeks there was a significantly higher mineralization (p=0.036) following the application of the bioactive form alone. This study showed significantly higher mineralization after use of a P-15 bioactivated material at early stages. Thus, it can be concluded that the application of the P-15 sequence to an hydroxyapatite accelerates the process of early bone formation, whereas no long-term effect was traced.

Animals↗

Expression of bone morphogenic protein 2/4, transforming growth factor-beta1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis.

PURPOSE: For the surgical treatment of osteoradionecrosis after multimodal therapy of head-and-neck cancers, free vascular bone grafts are used to reconstruct osseous structures in the previously irradiated graft bed. Reduced, or even absent osseous healing in the transition area between the vascular graft and the irradiated graft bed represents a clinical problem. Inflammatory changes and fibrosis lead to delayed healing, triggered by bone morphogentic protein 2/4 (BMP2/4) and transforming growth factor (TGF)-beta(1). Given the well-known fibrosis-inducing activity of TGF-beta(1), an osteoinductive effect has been reported for BMP2/4. However, the influence of irradiation (RT) on this cytokine expression remains elusive. Therefore, the aim of the present in vivo study was to analyze the expression of BMP2/4, TGF-beta(1), collagen I, and osteocalcin in the transition area between the bone graft and the graft bed after RT. METHODS AND MATERIALS: Twenty Wistar rats (male, weight 300-500 g) were used in this study. A free vascular tibia graft was removed in all rats and maintained pedicled in the groin region. Ten rats underwent RT with 5 x 10 Gy to the right tibia, the remainder served as controls. After 4 weeks, the previously removed tibia grafts were regrafted into the irradiated (Group 1) and nonirradiated (Group 2) graft beds. The interval between RT and grafting was 4 weeks. After a 4-week osseous healing period, the bone grafts were removed, and the transition area between the nonirradiated graft and the irradiated osseous graft bed was examined histomorphometrically (National Institutes of Health imaging program) and immunohistochemically (avidin-biotin-peroxidase complex) for the expression of BMP2/4, TGF-beta(1), collagen I, and osteocalcin. RESULTS: Absent or incomplete osseous healing of the graft was found in 9 of 10 rats after RT with 50 Gy and in 1 of 10 of the rats with nonirradiated osseous grafts. Histomorphometrically, the proportion of osseous healing in the transition area was 17% in Group 1 and 48% in Group 2 (p = 0.001). Compared with the nonirradiated rats, reduced enchondral and perichondral ossification was found in the healing area after RT, with a reduction of BMP2/4 and osteocalcin expression. TGF-beta(1) and collagen I expression in the transition area to the irradiated osseous graft bed was significantly increased compared with that in the nonirradiated osseous graft bed. CONCLUSION: After RT, osseous healing of vascular bone grafts is significantly reduced and may be a result of radiation-induced inhibition of BMP2/4 and osteocalcin expression. In addition, induction of TGF-beta(1) and collagen I expression occurs. Because the effects of the TGF-beta superfamily are manifold and partially unknown, additional research directions could be in the exogenous application of BMP2/4 and inhibition of TGF-beta(1) by antibody treatment to search for appropriate therapeutic approaches for improving osseous healing in the irradiated graft bed.

Animals↗

Neurophysiological monitoring of alveolar nerve function during sensor-controlled Er:YAG laser corticotomy in rabbits.

BACKGROUND AND OBJECTIVES: The sensor-controlled Er:YAG laser system may be a potent tool for tissue specific cutting in surgery. In order to investigate the impact of the laser on neural tissues, inferior alveolar nerve (IAN) function was monitored by the jaw-opening reflex (JOR) during specific corticotomy in rabbits. STUDY DESIGN/MATERIALS AND METHODS: Laser jaw corticotomy was performed in 13 anesthetized rabbits. During and after specific corticotomy the JOR was evoked by electric intraoral stimulation to monitor effects on IAN function. RESULTS: The JOR permanently abolished in one case and transiently failed immediately after surgery but largely recovered within days in another rabbit. In one experiment JOR threshold increased 7 days after corticotomy. Histology did not prove any objective nerve pathology. CONCLUSIONS: Monitoring IAN function by the JOR demonstrated the relatively low risk of nerve damaging during sensor-controlled laser corticotomy.

Animals↗

The CFSE distribution assay is a powerful technique for the analysis of radiation-induced cell death and survival on a single-cell level.

BACKGROUND AND PURPOSE: To analyze radiation sensitivity of cells and to monitor cellular responses to irradiation, sensitive test systems for cell death and proliferation on a single-cell level are required. Traditionally, cellular radiation survival is measured using the clonogenic assay as the gold standard. Here it is reported, that labeling of cells with 5-(and 6-)carboxyfluorescein diacetate succinimidyl ester (CFDASE) can be used as a highly sensitive assay to determine cellular response toward irradiation on a single-cell level. MATERIAL AND METHODS: The human malignant cell lines U937 (myelomonocytic, nonadherent), SW48 and SW480 (colorectal, adherent) were labeled with CFDASE, irradiated with either UVB (0-540 mJ/cm(2)), or X-rays (0-16 Gy). Cell death and proliferation were monitored by cytofluorometry and compared to the clonogenic assay for adherent SW48 and SW480 cells. RESULTS: Dividing nonadherent U937 cells displayed a shift in carboxyfluorescein (CF) fluorescence in parallel with an increased cell count indicating cell proliferation. By comparison, UVB-irradiated U937 cells did not show a shift in CF fluorescence and an increase in cell count indicating cell-cycle arrest. In a mixed cell culture, only the nonirradiated cells divided and concomitantly reduced their fluorescence. Calculating the number of cell divisions it was observed that the nonirradiated cells underwent approximately six cell divisions within 7 days, whereas the irradiated cells divided only once on average. The adherent SW480 colorectal cells showed a more pronounced cell-cycle arrest after irradiation with 240 mJ/cm(2) UVB as compared to cells treated with X-ray up to 16 Gy. Furthermore, the CFSE assay also discriminated colorectal cell lines of different intrinsic radiosensitivities and yielded results comparable to the standard clonogenic assay. CONCLUSION: Analysis of CF distribution can be employed as a powerful add-on to the clonogenic assay to simultaneously monitor cellular responses toward irradiation on a single-cell level. It constitutes an add-on to the clonogenic assay, especially for nonadherent cells.

Cell Adhesion↗

Restricted-expressed proliferation-associated protein (Repp86) expression in squamous cell carcinoma of the oral cavity.

PURPOSE: To determine the expression of repp86 (restricted-expressed protein of 86 kDa theoretical molecular mass), a proliferation- associated protein expressed in S-, G(2)- and M-phases of the cell cycle, in samples of normal mucosa as well as squamous cell carcinoma of the oral cavity (OSCC). PATIENTS AND METHODS: The repp86 labeling index (LI) was determined imunohistochemically in ten samples of normal oral mucosa and 59 samples of OSCC. Repp86 LI was correlated with tumor stage, histopathologic grading, and the expression of Ki-67 and topoisomerase IIalpha. RESULTS: Repp86 was detectable in all tissues analyzed. The mean LI was 4.7% for normal mucosa and 18.4% for squamous cell carcinoma (p < 0.0001). Repp86 expression was not related to tumor size, lymph node invasion, or histopathologic grading but was positively correlated with Ki-67 index (r = 0.48; p < 0.01) as well as with topoisomerase IIalpha (r = 0.39; p < 0.01). Ki-67 and topoisomerase IIalpha levels were also significantly correlated with each other (r = 0.34; p < 0.05). CONCLUSION: These results indicate that repp86 expression can be an additional proliferation marker among Ki-67 and topoisomerase IIalpha in OSCC. Further research will be directed at the evaluation of the prognostic value of repp86 expression in OSCC as well as in leukoplakia and early-stage OSCC.

Adult↗

Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite.

PURPOSE: This animal study examined the de novo bone formation in bony defects following the insertion of autogenous bone alone versus an injectable nanoparticle hydroxyapatite alone and in combination with 25% autogenous bone. The regenerative potentials of the tested materials were compared with each other. MATERIALS AND METHODS: A model with biological similarity to humans with regard to bone regeneration was a prerequisite for the transferability of the results to clinical practice. Therefore, the adult domestic pig was the animal of choice. A total observation period of 6 months was selected. Microradiographic and histologic evaluation of the bone specimens was completed at 8 defined times. RESULTS: Microradiography indicated mineralization rates in the 2 bone substitute groups that were not significantly lower than those found in the autogenous bone group. Histologically, there was suitable osseointegration and osteoconduction of the used material. Complete resorption of the nanoparticle hydroxyapatite had taken place after 12 weeks. CONCLUSIONS: It can be concluded that the evaluated nanoparticular hydroxyapatite met the clinical requirements for a bone substitute material within the limits of this experimental setting. Due to its microstructure, complete resorption took place during the course of this study.

Absorbable Implants↗

Stability of autogenous bone grafts after sinus lift procedures: a comparative study between anterior and posterior aspects of the iliac crest and an intraoral donor site.

BACKGROUND: Autologous bone is the standard material used for augmentations in oral-maxillofacial surgery. Depending on the origin of the graft, subsequent bone resorption may vary. STUDY DESIGN: This prospective study evaluated 57 patients receiving 2-stage sinus floor augmentations. Monocortical samples were taken at the site of bone harvesting, including the posterior (n = 28) and anterior pelvic (n = 15) and retromolar (n = 14) regions. At second-stage surgery, 6 months after the implant insertion, bone cores were harvested at the site of implant placement. All samples were analyzed by microradiography. RESULTS: Mean retromolar mineralization was 68.7% +/- 8.75%; 35.1% +/- 7.6% in the anterior and 30.7% +/- 9.5% in the posterior iliac crest. Areas augmented with grafts originating from the retromolar region showed a significant decrease to 53.0% +/- 5.15% (P = .001). A stable mineralization of 36.1% +/- 7.59% was found in sites where bone grafts from the anterior pelvic crest were used. Grafts from the posterior pelvis showed a slight increase to 34.5% +/- 6.5%. CONCLUSION: This prospective clinical study demonstrates the differences in mineralization depending on the origin of autogenous bone. Even after 6 months, these values could still be correlated to the transplants origin.

Alveolar Ridge Augmentation↗

Ewing sarcoma of the mandible in a child: interdisciplinary treatment concepts and surgical reconstruction.

Ewing's sarcoma is the second most common primary bone malignancy in childhood and adolescence. We present a standardized interdisciplinary treatment protocol according to the EURO-E.W.I.N.G. 99 study, applied in the treatment of a 7-year-old patient with localized Ewing's sarcoma of the left mandible. After six blocks of VIDE (vincristine/ifosfamide/doxorubicin/etoposide) chemotherapy and stem cells rescue, intensity modulated external radiation with 48.6 Gy and subsequent high dose therapy with busulphan-melphalan were administered. Tumor resection and immediate bony reconstruction was performed using a microvascular fibula graft 10 weeks after radiation. Because of the effective neoadjuvant treatment, no extensive soft tissue resection was necessary. Healing of the osteosynthesis was uneventful. No local or systemic recurrence and no signs of significant facial deformity were found after 12 month follow-up. The presented case underlines the requirement for multidisciplinary protocols involving radiologists, pathologists, oncologists, radiation oncologists, and surgeons for accurate diagnosis and appropriate therapy. To preserve cosmetics and function within the craniofacial area after tumor resection in children, microvascular reconstructive procedures can be successfully performed with a vascularized fibular graft.

Antineoplastic Combined Chemotherapy Protocols↗

Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy.

MAGE genes are silent in normal tissues except testis but are expressed in a variety of neoplastic lesions, and therefore represent ideal targets for immunotherapy. We analysed the expression of 6 MAGE-A genes (MAGE-A1 to -A6) to determine potential implications of these antigens as targets for immunotherapy in oral squamous cell carcinoma (OSCC). Oral tumor specimens (n=21) and non-neoplastic tissue samples (n=10) of oral mucosa from healthy patients were examined by a highly sensitive reverse transcription-nested polymerase chain reaction (MAGE-1- to -6 assay) which detect any cancer cells that express at least one of six MAGE subtype genes and allows also the identification of individual MAGE isotypes (M1 to M6). MAGE expression was restricted to neoplastic specimens. No expression of MAGE was observed in the non-neoplastic normal oral mucosal tissues. Fifteen of 21 (71%) oral carcinomas expressed at least one of MAGE-A1 to -6. The expression pattern of subtypes was heterogeneous: 62% of the tumor patients were positive for MAGE-3, 57% for MAGE-4, 48% for MAGE-6, 43% for MAGE-1, 38% for MAGE-2 and 24% for MAGE-5. Also coexpression of the genes could be determined: 13 (62%) coexpressed two, 10 (48%) coexpressed three, 8 (38%) coexpressed four, 6 (29%) coexpressed five and 5 coexpressed six of the 6 subtypes tested. The high incidence of MAGE expression in oral cancer indicates that monitoring of MAGE-A subtype expression in OSCC may be of potential interest to determine new immunotherapeutic targets and may be a possibility of specific immunotherapy with polyvalent anti-genes for this disease.

Antigens, Neoplasm↗

Exogenous modulation of TGF-beta(1) influences TGF-betaR-III-associated vascularization during wound healing in irradiated tissue.

BACKGROUND AND PURPOSE: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)beta isoforms following surgery in irradiated graft beds. Altered levels of TGF-beta(1) are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-beta receptor-III (TGF-betaR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-beta(1) treatment on TGF-betaR-III-associated vascularization in the transition area between irradiated graft bed and graft. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n = 16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 micro g anti-TGF-beta(1) into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-betaR-III and E-selectin expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. RESULTS: A significantly higher expression of TGF-betaR-III was seen in the irradiated and anti-TGF-beta(1)-treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-betaR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-beta(1)-treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher in the TGF-beta(1)-treated group. CONCLUSION: Neutralizing of TGF-beta(1) activity in irradiated tissue undergoing surgery leads to a higher expression of TGF-betaR-III and increased vascularization. TGF-betaR-III seems to be associated with newly formed blood vessels during neovascularization in wound healing.

Animals↗