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Monika Raab,
Sven Kappel,
Andrea Krämer,
Mourad Sanhaji,
Yves Matthess,
Elisabeth Kurunci-Csacsko,
Julia Calzada-Wack,
Birgit Rathkolb,
Jan Rozman,
Thure Adler, [......],
Eckhard Wolf,
Nicole Sänger,
Florian Prinz,
Martin de Angelis,
Jost Seibler,
Juping Yuan,
Martin Bergmann, Rainald Knecht,
Bertolt Kreft,
Klaus Strebhardt
Nature Communications 07/2011; 2:395. · 7.40 Impact Factor
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Monika Raab,
Sven Kappel,
Andrea Krämer,
Mourad Sanhaji,
Yves Matthess,
Elisabeth Kurunci-Csacsko,
Julia Calzada-Wack,
Birgit Rathkolb,
Jan Rozman,
Thure Adler, [......],
Eckhard Wolf,
Nicole Sänger,
Florian Prinz,
Martin Hrabě de Angelis,
Jost Seibler,
Juping Yuan,
Martin Bergmann, Rainald Knecht,
Bertolt Kreft,
Klaus Strebhardt
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ABSTRACT: High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions.
Nature Communications 01/2011; 2:395. · 7.40 Impact Factor
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ABSTRACT: Polo-like kinase 1 (Plk1) plays a pivotal role in the regulation of cellular proliferation. Plk1 is overexpressed in approximately 80% of human tumors of diverse origins, and overexpression of Plk1 promotes neoplastic transformation of human cells. A growing body of evidence suggests that deregulation of Plk1 closely correlates with prognosis of various cancers in humans. Thus, accurate assessment of Plk1 deregulation would provide clear clinical advantages. However, because of the limited amount of cancer tissues available, quantification of the Plk1 activity has not been feasible. Here, we report the development of a rapid, highly sensitive, and specific ELISA-based Plk1 assay that can quantify the level of Plk1 activity with a small amount (2-20 microg) of total cellular proteins. Unlike the conventional immunocomplex kinase assay, this assay directly utilizes total cellular lysates and does not require a Plk1 enrichment step such as immunoprecipitation or affinity purification. Using this assay, we demonstrated that Plk1 activity is elevated in tumors but not in the surrounding normal tissues and that the level of Plk1 activity significantly diminishes after an antiproliferative chemotherapy. The method described here may provide an innovative tool for assessing the predisposition for cancer development, monitoring early tumor response after therapy, and estimating the prognosis of patients with cancers from multiple organ sites.
Proceedings of the National Academy of Sciences 02/2009; 106(6):1725-30. · 9.68 Impact Factor
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ABSTRACT: Bortezomib has recently become the new treatment standard for relapsed or refractory multiple myeloma. We previously demonstrated that bortezomib also had a significant growth-inhibiting and apoptotic effect on squamous cell carcinoma of the head and neck (SCCHN) cells in vitro. Preclinical evidence has provided a rationale for combining bortezomib with dexamethasone in multiple myeloma, suggesting that the therapeutic effects of the two agents might be additive. These findings are in contrast with the results achieved in solid tumor models where the addition of dexamethasone reduced the efficacy of other antineoplastic drugs. In the present study, we investigated the effect of dexamethasone in combination with bortezomib in SCCHN cell lines for the first time. The antiproliferative effect of bortezomib alone or in combination with increasing concentrations of dexamethasone was investigated in four SCCHN cell lines. Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Bortezomib alone inhibited the growth of all four SCCHN cell lines significantly (p<0.047). The addition of dexamethasone leads to a clear tumor cell decline and showed a trend in enhancing the growth-inhibitory effect of bortezomib although the difference failed to reach statistical significance (p>0.05). Our first results show that dexamethasone increased the cytotoxic activity of bortezomib in most SCCHN cell lines investigated. These findings might be dependent on molecular factors such as the degree of tumor cell differentiation and proliferation rate. Therefore, further studies will be required to elucidate these molecular factors to substantiate our findings from a cancer biological point of view.
Oncology Reports 11/2008; 20(5):1207-11. · 1.84 Impact Factor
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ABSTRACT: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade) in combination with cetuximab in squamous cell carcinoma cell lines (SCC).
Dose-escalation studies were performed in five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in combination. Cell survival and growth inhibition were measured quantitatively using an MTT and LDH assay.
Bortezomib alone showed a significant antiproliferative activity in all SCC cell lines (P < 0.042), and the activity was further significantly enhanced by the addition of cetuximab (P < 0.043).
Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and cetuximab might be less toxic than conventional drug regimens used in the treatment of these tumors.
Journal of Cancer Research and Clinical Oncology 10/2008; 135(3):387-93. · 2.56 Impact Factor
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ABSTRACT: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade((R))) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).
Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.
Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P </= 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).
Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.
Journal of Cancer Research and Clinical Oncology 03/2008; 134(3):323-30. · 2.56 Impact Factor
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ABSTRACT: Primary non-Hodgkin lymphoma (NHL) of the paranasal sinuses is a rare neoplasm that cannot be easily diagnosed and differentiated as its clinical, histological, and imaging features are similar to those of other inflammatory and tumorous diseases in their early stages. We evaluated the morphological and functional imaging characteristics of primary NHL of the sphenoid sinus using CT and MR imaging. Morphological CT and MR imaging as well as perfusion CT imaging and proton MR spectroscopy (PRESS technique, TE = 135) was performed in three patients with the histological diagnosis of highly malignant primary B cell lymphoma of the sphenoid sinus. In all patients an inhomogeneous contrast agent enhancement as well as bony erosion of the sphenoid sinus was identified in CT and MR sections. In one patient an infiltration of the adjacent dura was present. The mean blood flow of the lymphomas was 135 ml/min per 100 g tissue, the mean blood volume was 8.06 ml/min, while the mean transit time and the mean permeability surface area product values were 5.11 s and 26.53 ml/min per 100 g, respectively. The mean choline to creatine ratio in the proton MR spectroscopy was 5.7. Cross-sectional imaging findings are not sufficient to establish the diagnosis of a primary NHL in the sphenoid sinus. Physiologic imaging offers valuable information that may be characteristic of the tumor. Future studies may lead to a safe differentiation of the lymphomas from other pathologic entities based on the combination of morphological and functional imaging.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 11/2007; 264(10):1207-13. · 1.29 Impact Factor
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ABSTRACT: Docetaxel has recently taken part in new chemotherapy regimens with promising activity especially in the first line therapy (induction chemotherapy) of head and neck cancer (SCCHN). Nevertheless a major problem concerning the response of SCCHN to chemotherapy is the high percentage of resting cells (G0-phase cells) being resistant to chemotherapy. To overcome this phenomenon we have investigated the capacity of several cytokines to switch on cells into division cycle and progress to the chemosensitive phases (S, M-phase).
Il-6, Serotonin, G-CSF and EGF were used to stimulate G0-phase squamous cell cancer cells (Detroit 562, A431, UM-SCC 10B) for reentry in the cell cycle to enhance the response to docetaxel. The proportion of G0-phase cells was detected through multicolor FACS analysis and Ki67 staining.
Cell cycle reentering was most effective after combination treatment with Serotonin+EGF. The proportion of G0 phase cells was significantly reduced after stimulation with Serotonin+EGF (p<0.05). Corresponding to cell cycle reentry the cytotoxic effect of docetaxel was significantly (p<0.04) enhanced in the prestimulated cells compared to the control (docetaxel monotreatment).
Our investigations demonstrate for the first time that sensitizing G0 phase squamous cell carcinoma cells for docetaxel treatment is possible by prestimulation with target cytokines. Considering that up to 95% of tumor cells are in the resting (G0) phase of the cell cycle at the initiation of chemotherapy, prestimulation with EGF and serotonin could contribute to a synchronization of cancer cells. This would clearly enhance the cytotoxic effect.
European Journal of Cancer 08/2007; 43(10):1502-7. · 5.54 Impact Factor
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Mehran Baghi,
Jens Wagenblast,
Markus Hambek,
Andreas Radeloff,
Wolfgang Gstoettner,
Agmal Scherzed,
Birgit Spaenkuch,
Juping Yuan,
Stefan Hornung,
Klaus Strebhardt, Rainald Knecht
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ABSTRACT: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups.
Patients' relatives were assessed using an anonymous self-report questionnaire that was established in our department by expanding on a questionnaire for cancer patients' relatives from the psycho-oncologic society in Switzerland. The evaluation was multidimensional, cancer specific, and relative based.
Relatives feel confronted themselves with cancer, although indirectly. The majority of the respondents were of the opinion that simultaneous psychological care of the patients and for the caring relatives would be helpful to cope with the situation.
This study shows the significant impact of cancer on caring relatives of head and neck cancer patients. In our opinion, health services should become more aware of this potential to ensure that the needs of the involved patient relatives are met as well as those of the patients.
The Laryngoscope 05/2007; 117(4):712-6. · 1.75 Impact Factor
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ABSTRACT: We sought to evaluate the routine clinical use of perfusion computed tomography in the detection and differentiation of primary and recurrent oropharynx and oral cavity tumors as well as of nodal disease.
A total of 77 patients with primary cancer as well as suspected recurrent disease and lymph nodes were evaluated. A dynamic acquisition (4 x 6-mm slices) of the largest axial tumor surface was performed and the tumor blood flow (BF), blood volume (BV), and mean transit time (MTT) were calculated by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for permeability surface area product imaging (PS). Tumor volume was calculated and region of interest analysis was performed on the pathologic and normal tissue.
The mean BF, BV, and PS values in the primary tumors (77.48 mL/min/100 g tissue; 5.29 mL/min; 13.33 mL/min/100 g tissue, respectively) were highly significantly different (P < 0.01) than those obtained in the normal structures. Mean MTT values (9.01 seconds) also were significantly lowered in the tumors compared with normal tissue (P < 0.05). There was no statistical difference in the perfusion values between the primary and the recurrent tumors. Recurrent disease could be differentiated on the basis of BF (P < 0.05) from tissue changes after chemo-radiation-treatment (mean BF: 69.71 versus 45.31 mL/min/100 g tissue, respectively). Differentiation of the lymph nodes was not possible by means of perfusion values. Tumor volume did not significantly correlate with any perfusion parameter.
Perfusion CT of oropharyngeal and oral cavity cancer in clinical routine is feasible and helps outlining the malignant tissue as well as differentiating recurrent disease from nonspecific post-therapeutic changes.
Investigative Radiology 04/2007; 42(3):172-9. · 4.59 Impact Factor
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ABSTRACT: Prostaglandin E2 (PGE2) serum levels have been shown previously to be increased in tumor bearing mice as well as in patients with solid tumors; however, the impact on the course or stage of disease has not been shown. We hypothesized that PGE2 is strictly required for aggressive and especially early-stage tumors of the head and neck to provoke invasion and angiogenesis.
We analyzed the serum PGE2 levels of 100 patients with head and neck squamous cell carcinoma of different stages before and 1 year after treatment and compared the results with the serum levels of 40 healthy donors and the secretion profile of 8 different squamous cell carcinoma cell lines.
Our investigations showed a statistically significant inverse correlation between PGE2 serum levels and tumor stage. Furthermore, this effect has been reflected by the results of our cell culture analyses, which showed an inversely regulated PGE2 secretion into the medium during the process of proliferation. Interestingly, the serum levels of PGE2 were significantly downregulated 1 year after successful treatment.
We conclude that PGE2 serum level as an indicator for early-stage cancer of the head and neck may function as a tumor marker during the follow-up period.
Head & Neck 04/2007; 29(3):244-8. · 2.40 Impact Factor
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ABSTRACT: The purpose was to evaluate the efficacy of tumor volumetry on MRI as predictive of response to treatment with induction chemotherapy, comparing the results with endoscopy.
Fifty patients with advanced squamous cell carcinoma of the head and neck (SSCHN) who underwent MRI volumetry before and after neoadjuvant chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) were included in this study. The tumor volume was calculated by a slice-by-slice evaluation. With the standard software of a workstation, the area of the tumor was measured slice by slice using manual segmentation. To evaluate the efficacy of MRI volumetry, pretreatment volume was compared with pretreatment remission status as evaluated with endoscopy.
Forty-five (90%) patients demonstrated a tumor downstaging after chemotherapy. Fourteen (28%) patients showed a complete histologic remission (CR), 31 (62%) patients showed a partial remission (PR). Pretreatment tumor volume was significantly different between patients whose tumor completely responded (CR) and those whose tumor did not completely respond or whose disease was stable or was progressive (p = .00023). We defined a threshold for the pretreatment tumor volume in patients with CR, which was equal to 29.71 cc.
We propose that MRI tumor volume analyses can be a useful parameter to predict the response to neoadjuvant chemotherapy in SCCHN.
Head & Neck 03/2007; 29(2):104-8. · 2.40 Impact Factor
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ABSTRACT: Benign and malignant neoplasms as well as metastatic lymph nodes of 39 patients were examined using localized single voxel magnetic resonance spectroscopy (MRS) [repetition time (TR) 1500, echo time (TE) 135) at 1.5 T. New techniques with simultaneous correction of motion artefacts during the acquisition, three-dimensional saturation pulses, respiratory triggering and smaller volume of interest (VOI) size, were applied. Ratios of peak areas under the choline (Cho) and creatine (Cr) resonances were estimated in all cases and compared with those from samples of normal tissue. Ninety one spectra were acquired in 39 patients, 63 of which were suitable for further evaluation. The smallest VOI was 0.40 cm(3). The Cho/Cr ratios in all malignant neoplasms (mean: 5.2, range: 1.7-17.8) were significantly elevated relative to those in the normal muscle structures (mean: 0.9, range: 0.2-1.4), while those in the benign neoplasms were elevated (mean: 24.4, range: 1.4-59.7) with respect to those in the malignant ones. The average Cho/Cr ratio in the metastatic lymph nodes was significantly higher (mean: 4.8, range: 3.3-5.6) than that for benign lymphoid hyperplasia (mean: 2.2, range: 1.0-3.0). MRS measurements were able to differentiate recurrent disease from post-therapeutic tissue changes in 11 out of 13 patients.
European Radiology 02/2007; 17(1):251-7. · 3.22 Impact Factor
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ABSTRACT: The aim of this project was to design, develop, and implement a head and neck cancer computer database for clinical and scientific use.
A relational database based on Filemaker Pro 6.0 was developed and integrated into our local network. A precise and easy-to-handle interface should allow for a quick overview of the patient's oncological history and for optimized data acquisition. An automatic report function was integrated to enhance the quality of daily patient care. For evaluation purposes, statistical analysis functions were implemented.
Over a 14-month period, 410 patient records were available through the local network. The automated report function and the well-organized screen desktop resulted in time-efficient and accurate patient care. Additionally, the quality of information presented to referring physicians increased notably. The statistical analysis data provided by the database were reliable and easy to export.
We developed an oncology database for both clinical and scientific purposes and integrated it successfully into our patient documentation system. The combination of clinical and scientific features proved to be very effective in daily routine and research.
The Annals of otology, rhinology, and laryngology 03/2006; 115(2):144-9. · 1.05 Impact Factor
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ABSTRACT: The proto-oncogene pituitary tumor-transforming gene (PTTG) has been shown to be abundantly overexpressed in a large variety of neoplasms likely promoting neo-vascularization and tumor invasiveness. In this study, we investigated a potential role for PTTG mRNA expression as a marker to evaluate the future clinical outcome of patients diagnosed with primary cancer of the head and neck.
Tumor samples derived from primary tumors of 89 patients suffering from a squamous cell carcinoma were analyzed for PTTG mRNA-expression and compared to corresponding unaffected tissue. Expression levels were correlated to standard clinico-pathological parameters based on a five year observation period.
In almost all 89 tumor samples PTTG was found to be overexpressed (median fold increase: 2.1) when compared to the unaffected tissue specimens derived from the same patient. The nodal stage correlated with PTTG transcript levels with significant differences between pN0 (median expression: 1.32) and pN+ (median expression: 2.12; P = 0.016). In patients who developed a tumor recurrence we detected a significantly higher PTTG expression in primary tumors (median expression: 2.63) when compared to patients who did not develop a tumor recurrence (median expression: 1.29; P = 0.009). Since the median expression of PTTG in patients with tumor stage T1/2N0M0 that received surgery alone without tumor recurrence was 0.94 versus 3.82 in patients suffering from a tumor recurrence (P = 0.006), PTTG expression might provide a feasible mean of predicting tumor recurrence.
Elevated PTTG transcript levels might be used as a prognostic biomarker for future clinical outcome (i.e. recurrence) in primary squamous cell carcinomas of the head and neck, especially in early stages of tumor development.
BMC Cancer 02/2006; 6:242. · 3.01 Impact Factor
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ABSTRACT: The comparison of gene expression measurements obtained with different technical approaches is of substantial interest in order to clarify whether inter-platform differences may conceal biologically significant information. To address this concern, we analyzed gene expression in a set of head and neck squamous cell carcinoma patients, using both spotted oligonucleotide microarrays made from a large collection of 70-mer probes and commercial arrays produced by in situ synthesis of sets of multiple 25-mer oligonucleotides per gene. Expression measurements were compared for 4425 genes represented on both platforms, which revealed strong correlations between the corresponding data sets. Of note, a global tendency towards smaller absolute ratios was observed when using the 70-mer probes. Real-time quantitative reverse transcription PCR measurements were conducted to verify expression ratios for a subset of genes and achieved good agreement regarding both array platforms. In conclusion, similar profiles of relative gene expression were obtained using arrays of either single 70-mer or multiple short 25-mer oligonucleotide probes per gene. Although qualitative assessments of the expression of individual genes have to be made with caution, our results indicate that the comparison of gene expression profiles generated on these platforms will help to discover disease-related gene signatures in general.
Laboratory Investigation 09/2005; 85(8):1024-39. · 3.64 Impact Factor
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ABSTRACT: Recent studies on polychemotherapy of head and neck cancer showed an improved remission rate on adding taxanes to the standard cytotoxic drugs cisplatin and 5-fluorouracil (5-FU). Moreover, for enhancing the response rate of chemotherapy today, a series of biological response modifiers are of interest, including modulators of the epidermal growth factor receptor (EGFR). Therefore we investigated whether the addition of monoclonal antibodies against the EGFR could enhance the response rate of cisplatin, 5-FU and docetaxel. Squamous cell cancer lines were transplanted into nude mice. After tumors had begun to grow, they were treated either with cisplatin, 5-FU or docetaxel alone or in combination with escalating doses of a humanized monoclonal anti-EGFR antibody.
Advances in oto-rhino-laryngology 02/2005; 62:81-91.
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ABSTRACT: RNA interference initiated by small interfering RNAs effectively suppresses gene expression, but the suppression is transient, which limits the therapeutic use of this technique. Polo-like kinase 1 (PLK1) is a key cell cycle regulator that is overexpressed in various human tumors. We used a xenograft mouse model to determine whether an RNA interference-based strategy that used short hairpin RNAs (shRNAs) to suppress PLK1 expression could inhibit tumor growth in vivo.
HeLa S3 cervical and A549 lung cancer cell lines were transfected with plasmids containing U6 promoter-driven shRNAs against human PLK1 or control (parental or scrambled) plasmids. Plasmids were treated with the nuclease inhibitor aurintricarboxylic acid (ATA) as protection against nucleases in murine blood. Nude mice carrying xenograft tumors were injected with shRNA plasmids, and their xenograft tumor growth was assessed. Northern and western blot analyses were used to measure PLK1 mRNA and protein expression, respectively, in transfected cultured cells and in xenograft tumors. All statistical tests were two-sided.
Levels of PLK1 mRNA and protein were lower in HeLa S3 and A549 cancer cells transfected with PLK1 shRNA plasmids than in corresponding cells transfected with control parental or scrambled PLK1S shRNA plasmids. Proliferation of cells transfected with PLK1 shRNA was lower than that of cells transfected with either control plasmid, and proliferation of cells transfected with ATA-treated PLK1 shRNA plasmids was even lower. In mice with human xenograft tumors, PLK1 shRNA expression from ATA-treated plasmids reduced tumor growth to 18% (95% confidence interval [CI] = 12% to 26%; P =.03) and from untreated plasmids reduced tumor growth to 45% (95% CI = 26% to 64%; P =.1) of that of tumors in mice treated with scrambled control PLK1S shRNA plasmids.
The combination of shRNA-mediated gene silencing with effective in vivo gene delivery strategies appears to generate a long-lasting silencing signal.
CancerSpectrum Knowledge Environment 07/2004; 96(11):862-72. · 14.07 Impact Factor
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ABSTRACT: To evaluate the role of hypoxia in cholesteatoma progression.
Immunohistochemical analysis of paraffin-embedded human specimens.
Thirteen middle ear cholesteatomas and 10 samples of normal human external ear canal skin were stained immunohistochemically for the presence of hypoxia inducible factor 1 alpha (HIF 1 alpha) and Von Hippel Lindau protein. Specimens were then analyzed semiquantitatively.
Staining for both antibodies could be detected in all cholesteatomas (perimatrix and matrix), as well as in the samples of normal human ear canal skin. Cholesteatoma specimens showed statistically significant increased staining when compared with normal human skin and mucosa. The age of patients and relapse surgery affected immunohistochemical staining of HIF 1 alpha and Von Hippel Lindau protein.
Elevated staining intensities for HIF 1 alpha and Von Hippel Lindau protein in cholesteatoma tissue indicated that cholesteatoma may be hypoxic. In addition, our data indicated that relapse cholesteatomas yield a higher degree of hypoxia than ears without surgery.
The Laryngoscope 08/2003; 113(7):1210-5. · 1.75 Impact Factor
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ABSTRACT: Recent studies demonstrated that tumors overexpressing the epidermal growth factor receptor (EGF-R, erbB-1) are associated with poor clinical outcome. This led to the development of a variety of monoclonal antibodies targeting the extracellular domain of this receptor tyrosine kinase. The aim of our study was the evaluation of anti-EGF-R antibody EMD 55900 therapy for treatment of breast cancer. On the basis of 299 tumor specimens derived from breast cancer patients, we investigated EGF-R expression and generated a collective of primary xenotransplants in athymic nude mice. The animals received therapy in 2 treatment schedules to investigate the therapeutic response in early stages of tumor formation as well as on well established tumors. Using 6 different tumors with EGF-R expression levels between 10-300 fmol/mg total protein, we found a therapeutic effect when the EGF-R expression of the tumors was at least 40 fMol/mg. On the basis of these experimental data and our EGF-R expression analysis of breast cancer specimens, we conclude that up to 15% of breast cancer patients could benefit from this monotherapy with EMD 55900.
International Journal of Cancer 11/2002; 101(4):390-4. · 5.44 Impact Factor
