Biomedical subjects

Markus Hambek

Publications and source records attributed to Markus Hambek.

15 recordsLinked to original sources

PubMed2007

Usefulness of MRI volumetric evaluation in patients with squamous cell cancer of the head and neck treated with neoadjuvant chemotherapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: We propose that MRI tumor volume analyses can be a useful parameter to predict the response to neoadjuvant chemotherapy in SCCHN.

Adult↗

PubMed2007

Inverse correlation between serum PGE2 and T classification in head and neck cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Biomarkers, Tumor↗

PubMed2006

AdOnco: a database for clinical and scientific documentation of head and neck oncology.

OBJECTIVES: The aim of this project was to design, develop, and implement a head and neck cancer computer database for clinical and scientific use. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Algorithms↗

PubMed2005

Patient-based cross-platform comparison of oligonucleotide microarray expression profiles.

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.

Base Sequence↗

PubMed2005

EGFR-antibody-supplemented TPF chemotherapy. Preclinical investigations to a novel approach for head and neck cancer induction treatment.

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.

Animals↗

PubMed2004

Cochlear implantation via the round window membrane minimizes trauma to cochlear structures: a histologically controlled insertion study.

OBJECTIVE: To evaluate cochlear implant trauma to intracochlear structures when inserting the electrode via the round window membrane. MATERIAL AND METHODS: Eight fresh human temporal bones were evaluated histologically after insertion using two types of cochlear implant array. Bones underwent a special fixation and embedding procedure that allowed sectioning of undecalcified bone with the electrode in situ. Insertions depths were evaluated radiologically and histologically. RESULTS: All arrays were found in the scala tympani of the cochlea. Basal trauma could be avoided in all but one specimen. The mean depth of insertion was 382.5 degrees. Apically, only one implanted bone showed cochlear trauma exceeding lifting of the basilar membrane. CONCLUSION: Insertions through the round window membrane were shown to be atraumatic, even in basal cochlear regions. This route of insertion might be very effective for combined electric and acoustic stimulation of the auditory system.

Cochlea↗

PubMed2004

Preservation of basal inner ear structures in cochlear implantation.

The aim of this report was to examine basal trauma in implanted human temporal bones and discuss modified approaches to the basal cochlear turn to avoid destruction of basal cochlear structures. Thirty-three human temporal bones were implanted with four different cochlear implant electrode arrays manufactured by MED-EL using either a caudal approach cochleostomy or round window membrane insertions. All specimens were processed with a special histological technique that allows sectioning of undecalcified bone with the electrode in situ. All bones were evaluated histologically in terms of basal cochlear trauma. Two pathomechanisms of basal trauma could be distinguished and were evaluated separately, buckling of the basal end of the array and trauma by drilling. Using the caudal approach cochleostomy, the total percentage of destructive basal trauma was 48% compared to less than 15% when performing round window membrane insertions. Although it is still unclear whether basal cochlear trauma influences apical cochlear function or not, adapted surgical procedures and no forceful insertion maneuvers should be used when performing cochlear implantations with hearing preservation.

Cochlea↗

PubMedDate not supplied

EGFR antibody-supplemented TPE-chemotherapy. Preclinical investigations to a novel approach for head and neck cancer induction treatment.

Recent studies on polychemotherapy of head and neck cancer have shown 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 transplated on nude mice. After tumors had begun to grow, they were treated either with cisplatin, 5-FU and docetaxel alone or in combination with escalating doses of a humanized monoclonal anti-EGFR antibody. Comparing with controls, docetaxel alone as well as the combination of docetaxel, cisplatin and 5-FU resulted in a significant tumor growth delay. The antibody alone also slowed down the tumor growth significantly at each concentration. Nevertheless, neither chemotherapy agents nor antibody alone yielded complete tumor remissions over an observation period up to 6 weeks. Only the combination of cisplatin, 5-FU, docetaxel and the antibody resulted in highly significant complete tumor remissions. Therefore we can show for the first time that the effect of TPF, which is now used as a novel Phase II protocol for induction chemotherapy in head and neck cancer, could be highly significantly enhanced through the addition of anti-EGFR antibodies. Because we did not observe an increased toxicity in the animal experiments, TPF/anti-EGFR therapy may define a new strategy in the induction treatment of head and neck carcinomas.

Animals↗

PubMedDate not supplied

STAT 3 activation in head and neck squamous cell carcinomas is controlled by the EGFR.

Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on epidermal growth factor receptor (EGFR) expression. As STAT 3 activation as well contributes to the cell growth in SCCHN, the interaction of STAT 3 and the EGFR is of great interest when considering treatment options through inhibition of STAT 3. We, therefore, evaluated the influence of blocking or activating the EGFR in human SCCHN cell lines and in vivo tumors on STAT 3 activation. We compared the effects on STAT 3 activation with the regulation of MAP Kinase under these conditions. We found that STAT 3 can be strongly inhibited via EGFR blocking in vitro as well as in vivo. However, the influence of EGFR regulation on the MAP Kinase pathway seemed to be very slight. These findings provide evidence that STAT 3 signal activity in head and neck carcinomas, which is partially responsible for proliferative activity, can be controlled via the EGFR.

Animals↗

PubMedDate not supplied

The efficacy of MRI with ultrasmall superparamagnetic iron oxide particles (USPIO) in head and neck cancers.

BACKGROUND: The objective was to evaluate the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) compared to plain MRI in patients with a clinical N+ neck using histology as a gold standard. MATERIALS AND METHODS: Twenty-eight patients underwent unenhanced and USPIO-enhanced MRI using T1-weighted spin echo (SE) sequences and high resolution Turbo-Spin-Echo (TSE) T2-weighted sequences, as well as T2-weighted Gradient Echo (GE) sequences in axial and sagittal slice orientation. The signal intensity (SI) decrease was measured by a region of interest evaluation and visual analysis was performed. RESULTS: Histopathological evaluation of 363 lymph nodes revealed 34 as metastatic. USPIO MRI detected 28 metastases (sensitivity 82.3%) and 329 non-metastatic lymph nodes (specificity 100%). Regarding lymph node size, USPIO MRI was correct in all patients who underwent surgery. One lymph node with microinfiltration of tumor cells was detected by USPIO MRI. CONCLUSION: There were no side-effects during or after application of the contrast agent. This study confirms the efficacy of MRI with USPIO in patients with head and neck cancer. USPIO-enhanced MRI could have an important effect on surgery planning. Because of its high specificity, USPIO-enhanced MRI seems to be a diagnostic modality able to differentiate borderline-sized lymph nodes.

Adult↗

PubMedDate not supplied

Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN).

Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on epidermal growth factor receptor (EGFR) expression. The EGFR activates different signal pathways leading to gene transcription in the nucleus due to cell cycle progression and proliferation of tumor cells. AKT, STAT3 and MAPK play central roles in these pathways. However, they are not only regulated by the EGFR. We therefore investigated whether a specific inhibitor of the EGFR tyrosine kinase (ZD 1839 or Iressa) is able to inhibit phosphorylation of these three signals at the same time. Western blot analysis of pretreated SCCHN cells revealed that ZD 1839 greatly reduces the amount of phosphorylated AKT, STAT3 as well as MAPK Surprisingly, this effect was not dose-dependent between the concentration range of 5.15 to 41.2 microM/ml. We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment.

Antineoplastic Agents↗

PubMedDate not supplied

Reduction of cisplatin dosage by ZD 1839.

Cisplatin (CDDP) is the main chemotherapeutic drug in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), but its nephrotoxicity often limits the treatment. ZD 1839 is an orally-applicable, selective EGFR tyrosine kinase inhibitor. This investigation explored whether the cisplatin dose can be reduced by the additional application of ZD 1839. Four different SCCHN cell lines were treated with descending doses of CDDP alone or in combination with ZD 1839. Proliferation was measured by the MTT assay; tumor cell toxicity was measured by using the lactate dehydrogenase approach. ZD 1839 augments CDDP-dependent antiproliferative effects. By adding ZD 1839 to the treatment regimen, the CDDP dose could be reduced by up to 25% of the CDDP IC50 dose without compromising the antiproliferative effect. Adding ZD 1839 to CDDP may therefore enable CDDP treatment at a lower dose without compromising antiproliferative effects.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Prestimulation of head and neck cancer cells with growth factors enhances treatment efficacy.

OBJECTIVES: In recent years, new chemotherapy regimens with promising activity, especially in first-line therapy (induction chemotherapy) of head and neck cancer (SCCHN), have been developed. 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, the capacity of several cytokines to switch on cells into the division cycle and progress to the chemosensitive phases (S-, M-phases) was investigated. MATERIALS AND METHODS: Interleukin-6, serotonin, granulocyte colony stimulating factor (G-CSF) and epidermal growth factor (EGF) were used to stimulate G0-phase squamous cell cancer cells (Detroit 562, A431, UM-SCC 10B) for re-entry into the cell cycle to enhance the response to cisplatin. The proportion of G0-phase cells was detected through multicolor FACS analysis and Ki-67 staining. RESULTS: Cell cycle re-entry 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 re-entry, the cytotoxic effect of cisplatin was significantly (p < 0.04) enhanced in the prestimulated compared to the control cells (cisplatin mono-treatment). CONCLUSION: Our investigations demonstrated for the first time that sensitizing G0-phase squamous cell carcinoma cells for chemotherapy 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.

Antineoplastic Agents↗

PubMedDate not supplied

Adjuvant docetaxel, cisplatin and 5-fluorouracil (TPF) in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: In this phase II study, the efficacy and toxicity of a triple chemotherapy with docetaxel, cisplatin and 5- Fluorouracil (TPF) was evaluated in the adjuvant therapy of locoregionally advanced cancer of the head and neck. This represented the first use of polychemotherapy as single adjuvant therapy after surgery. PATIENTS AND METHODS: Twenty patients with stage II-IV (UICC) squamous cell carcinoma of the head and neck (SCCHN) were treated by surgery of the primary and the regional lymph nodes. Four weeks after surgery, all patients received polychemotherapy consisting of docetaxel 75 mg/m2 day 1, cisplatin 100 mg/m2 day 1 and 5- Fluorouracil (5- FU) 1000 mg/m2 days 1 through 4 (total dose 4000 mg/m2), on days 1, 22 and 43 for a maximum of 3 cycles. The performance status of all patients at the beginning of the chemotherapy was 0-1 according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: Fifty-eight cycles were administered to the 20 patients. The major acute toxicities were mucositis (2 patients) and febrile neutropenia (4 patients). One patient dropped out after the first cycle because of severe mucositis. After a median follow-up of 16.5 months (range, 1-41 months), the median time to progression was 20 months (range, 16-22 months). The estimated overall survival according to Kaplan-Meier at the median time of follow-up was 90%. No distant metastases were detectable after the adjuvant chemotherapy with TPF in locally advanced SCCHN, neither were late effects observed. CONCLUSION: TPF was tolerated, with an acceptable toxicity profile, in patients with a good performance status. The preliminary results appear to justify further investigations to evaluate the efficacy of this modality in the adjuvant setting.

Adult↗

PubMedDate not supplied

A phase II trial of docetaxel, cisplatin and 5-fluorouracil in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).

BACKGROUND: In this phase II study, for the first time the efficacy and toxicity of triple chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with recurrent head and neck cancer was evaluated. PATIENTS AND METHODS: Twenty-four patients with stage IV (UICC) recurrent squamous cell carcinoma of the head and neck (SCCHN), with different tumor sites, were treated with a polychemotherapy consisting of docetaxel 75 mg/m2 day 1, cisplatin 100 mg/m2 day 1 and 5-fluorouracil (5-FU) 1000 mg/m2 days 1 through 4 (total dose 4000 mg/m2) on days 1, 22 and 43, for a maximum of 3 cycles. The performance status of all patients at the start of the chemotherapy was 0-2, according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: Sixty-eight cycles were administered to 24 patients. The reversible major acute toxicities were afebrile neutropenia in 6 patients and emesis in 4 patients. One patient died, probably because of myocardial infarction related to treatment. A remission was observed in 10 patients. Six patients showed a complete remission and 4 patients a partial remission. The median time to progression was 10 months (range, 4-42 months), the median overall survival after treatment was 13 months (range, 6-48 months) and the median recurrence-free survival was 12 months (range, 10-18 months). CONCLUSION: In terms of toxicity, TPF seems to be a feasible option for the treatment of recurrent SCCHN in patients with a compromised performance status. These results justify further investigations to evaluate the efficacy of this treatment.

Adult↗