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Petra Kopfmaier - One of the best experts on this subject based on the ideXlab platform.
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31p nmr spectroscopy of a xenografted Hypopharynx Carcinoma effects of tumor growth and treatment with cisplatin on the tumor phosphorus metabolism histology and cytokinetics
NMR in Biomedicine, 1992Co-Authors: R Tauschtreml, F Baumgart, Dieter Ziessow, Petra KopfmaierAbstract:A xenografted Hypopharynx Carcinoma growing subcutaneously in nude mice was studied by in vivo31P NMR spectroscopy during uninfluenced growth and following treatment with cisplatin (CDDP). Parallel to the NMR experiments, the cytokinetic and histological changes in the tumor were investigated. The most significant change in the growing tumor was a decline in the level of phosphocreatine (PCr), whereas the tumor pH did not change. Following treatment with CDDP (4, 8 and 12 mg/kg), a dose-dependent decrease in the level of phosphomonoesters (PME) took place, whilst no dose dependence could be observed for the increase of PCr. the pH shifted to alkaline only after administration of the highest CDDP dose. Tumor cytokinetics revealed a cell arrest at the G1/S boundary 24 h after chemotherapy. At this time, the histological sections showed a dilatation of capillaries, whereas first necroses appeared on day 3. The proliferative activity of the tumor showed a sharp decline 24 h after CDDP application, followed by a revival of cell proliferation that was proportional to the dose applied between days 5 and 7. This increase in proliferative activity was paralleled by a marked increase in the PME/phosphodiesters ratio. Thus, in the tumor investigated the PME were the best indicators of tumor response to therapy. A precise correlation between the cytokinetic data and the re-energization of the tumor was not possible because histological changes, which may contribute to improved tumor energy status took place at the same time.
Ricardo Sanz-fernández - One of the best experts on this subject based on the ideXlab platform.
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Paclitaxel-loaded polymeric nanoparticles based on α-tocopheryl succinate for the treatment of head and neck squamous cell Carcinoma: in vivo murine model
'Informa UK Limited', 2021Co-Authors: Juan Riestra-ayora, Carolina Sánchez-rodríguez, Raquel Palao-suay, María Rosa Aguilar, Joaquín Yanes-díaz, Ana Martín-hita, Ricardo Sanz-fernándezAbstract:The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects. A polymeric nanocarrier system was developed for the delivery of PTX to improve HNSCC treatment. This study aimed to evaluate the antitumor efficacy of PTX-loaded polymeric nanoparticles based on α-TOS (PTX-NPs) administered by direct intratumoral injection into a Hypopharynx Carcinoma squamous cells (FaDu) tumor xenograft mouse model. The nanocarrier system based on block copolymers of polyethylene glycol (PEG) and a methacrylic derivative of α-TOS was synthesized and PTX was loaded into the delivery system. Tumor volume was measured to evaluate the antitumor effect of the PTX-NPs. The relative mechanisms of apoptosis, cell proliferation, growth, angiogenesis, and oxidative and nitrosative stress were detected by Western blotting, fluorescent probes, and immunohistochemical analysis. The antitumor activity results showed that compared to free PTX, PTX-NPs exhibited much higher antitumor efficacy and apoptosis-inducing in a FaDu mouse xenograft model and demonstrated an improved safety profile. Ki-67, EGFR, and angiogenesis markers (Factor VIII, CD31, and CD34) expression were significantly lower in the PTX-NPs group compared with other groups (p
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α-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of Head and Neck Squamous Cell Carcinoma
'MDPI AG', 2018Co-Authors: Carolina Sánchez-rodríguez, Raquel Palao-suay, Laura Rodrigáñez, María Rosa Aguilar, Sergio Martín-saldaña, Julio San Román, Ricardo Sanz-fernándezAbstract:The aim of this work is to study, in an in vitro head and neck squamous cell Carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the newly synthetized α-TOS-loaded NPs in proliferating endothelial cells and Hypopharynx Carcinoma squamous cells and measured markers of angiogenesis, apoptosis and reactive oxygen species (ROS). α-TOS-loaded NPs suppressed angiogenesis by inducing accumulation of ROS and inducing apoptosis of proliferating endothelial cells. These NPs also decrease the number and quality of capillary-like tubes in an in vitro three-dimensional (3D) experiment, decrease the production of the pro-angiogenic vascular endothelial growth factor and down-regulate the expression of its receptor. The anti-migratory efficacy of α-TOS is corroborated in Hypopharynx Carcinoma cells by decreasing the secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting cell migration. These results confirm that α-TOS-based NPs not only present anticancer properties, but also antiangiogenic properties, therefore making them promising candidates for multi-active combinatorial anticancer therapy
R Tauschtreml - One of the best experts on this subject based on the ideXlab platform.
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31p nmr spectroscopy of a xenografted Hypopharynx Carcinoma effects of tumor growth and treatment with cisplatin on the tumor phosphorus metabolism histology and cytokinetics
NMR in Biomedicine, 1992Co-Authors: R Tauschtreml, F Baumgart, Dieter Ziessow, Petra KopfmaierAbstract:A xenografted Hypopharynx Carcinoma growing subcutaneously in nude mice was studied by in vivo31P NMR spectroscopy during uninfluenced growth and following treatment with cisplatin (CDDP). Parallel to the NMR experiments, the cytokinetic and histological changes in the tumor were investigated. The most significant change in the growing tumor was a decline in the level of phosphocreatine (PCr), whereas the tumor pH did not change. Following treatment with CDDP (4, 8 and 12 mg/kg), a dose-dependent decrease in the level of phosphomonoesters (PME) took place, whilst no dose dependence could be observed for the increase of PCr. the pH shifted to alkaline only after administration of the highest CDDP dose. Tumor cytokinetics revealed a cell arrest at the G1/S boundary 24 h after chemotherapy. At this time, the histological sections showed a dilatation of capillaries, whereas first necroses appeared on day 3. The proliferative activity of the tumor showed a sharp decline 24 h after CDDP application, followed by a revival of cell proliferation that was proportional to the dose applied between days 5 and 7. This increase in proliferative activity was paralleled by a marked increase in the PME/phosphodiesters ratio. Thus, in the tumor investigated the PME were the best indicators of tumor response to therapy. A precise correlation between the cytokinetic data and the re-energization of the tumor was not possible because histological changes, which may contribute to improved tumor energy status took place at the same time.
D A Clevert - One of the best experts on this subject based on the ideXlab platform.
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comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast enhanced ultrasound ceus in an experimental human squamous cell Carcinoma model
Clinical Hemorheology and Microcirculation, 2012Co-Authors: Philipp M Paprottka, Michael Ingrisch, A Koelln, Pamela Zengel, Clemens C Cyran, Konstantin Nikolaou, M Reiser, D A ClevertAbstract:PURPOSE To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-Carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS Human Hypopharynx-Carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.
Hans Edmund Eckel - One of the best experts on this subject based on the ideXlab platform.
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induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome delos i trial
European Archives of Oto-rhino-laryngology, 2009Co-Authors: Andreas Dietz, Hans Edmund Eckel, Volker Rudat, Jens Dreyhaupt, Maria Pritsch, Florian Hoppe, Rudolph Hagen, L Pfreundner, Ursula Schroder, Markus HessAbstract:A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/Hypopharynx Carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 Hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from Hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.
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surgical treatment for Hypopharynx Carcinoma feasibility mortality and results
Otolaryngology-Head and Neck Surgery, 2001Co-Authors: Hans Edmund Eckel, S Staar, P Volling, Christian Sittel, Michael Damm, Markus JungehuelsingAbstract:Abstract This study seeks to evaluate treatment modalities, mortality after surgery, survival, and local control rates for a consecutive cohort of patients with cancer of the Hypopharynx treated according to a prospective protocol that favors surgery as an initial approach to the disease. The charts of 228 consecutive patients with previously untreated hypopharyngeal squamous cell Carcinoma were reviewed. Outcome measures (overall survival, disease specific survival, and local control) were calculated using the Kaplan-Meier estimator. Of 228 consecutive patients, 136 (59.6%) were found suitable for initial surgical treatment. Of the remaining 92 patients, 18 (7.9%) had nonresectable lymph node metastases, 16 (7.0%) had unresectable primary tumors, 13 (5.7%) refused surgery, and 13 (5.7%) presented distant metastases during initial diagnostic evaluation. Of those who had surgery, 46 had larynx-sparing procedures, 54 had total laryngectomy, and 36 had total laryngo-pharyngectomy. None of the patients who had surgery died postoperatively. Actuarial 5-year overall survival was 27.2% for all 228 patients, 39.5% for the 136 patients with surgical treatment, and 61.1% for the 46 patients who were treated with larynx-sparing procedures. (Otolaryngol Head Neck Surg 2001;124:561-9)