Quantitative and qualitative analysis of integrin subtype expression in melanocytes and melanoma cells.

Objectives: Changes in the integrin expression pattern have been associated with the malignant transformation of melanocytes suggesting that integrins may be potential biomarkers as well as molecular targets for individualized therapy. Since there is a lack of comprehensive qualitative and quantitative expression data, we characterized the integrin expression profile in normal and malignant human cells of the melanocytic lineage.Methods: Seven melanoma cell lines as well as normal human melanocytes were investigated in western blots including recombinant integrin subunits for quantification.Results: Expression patterns were heterogeneous. In melanoma, overexpression of α4, α6, αL, ß5, and ß6 was found. Integrins α7, α9, and ß4 were overexpressed in a subset of the melanoma cell lines. Overexpression was defined as a lack of expression in melanocytes but expression in more than half (4) of the melanoma lines. 1.9 to 6.7 × 106 integrin molecules (about 0.3% of total cellular protein) were estimated to be expressed per cell. Expression of integrin αE at the protein level was found in melanoma and melanocytes, to the best of our knowledge, for the first time. Integrins αM and ß2 were not detected.Conclusion: Integrins α4, α6, αL, ß5, and ß6 appear to be overexpressed in melanoma cells. These subunits may serve as biomarkers and/or therapeutic targets.

Prognostic value of advanced lung cancer inflammation index in head and neck squamous cell carcinoma.

PURPOSE: The advanced lung cancer inflammation index (ALI) is a useful tool for prediction of outcome in several malignancies. However, to date, its significance in head and neck cancer patients has not been evaluated. METHODS: We retrospectively analyzed data from 93 patients who were diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with surgical resection and postoperative radiotherapy between 2002 and 2012. The aim of this study was to investigate whether the preoperative ALI is a prognostic indicator for disease-free survival and overall survival in HNSCC patients. RESULTS: A low ALI was significantly associated with a worse 5-year disease-free survival (47.0 vs. 83.5%, p < 0.001), and overall survival (44.4 vs. 73.6%, p = 0.008). Multivariate analysis showed that low ALI was independently associated with disease-free survival (p < 0.001) and overall survival (p = 0.02). CONCLUSION: The ALI could serve as an easily available prognostic indicator for disease-free and overall survival prediction in patients with HNSCC.

PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome.

AIMS: Expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not elucidated fully. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and the impact on patients' clinical outcome. METHODS AND RESULTS: Immunohistochemical staining patterns of PD-L1 and PD-1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated with patients' clinical data. PD-L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis, and correlates significantly with decreased overall survival (OS) (P = 0.01) and disease-free survival (DFS) (P = 0.001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with presence of lymph node metastasis (P = 0.0223). Infiltration of PD-1-expressing lymphocytes correlates significantly with favourable OS (P = 0.001) and DFS (P = 0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (P = 0.007) and DFS (P = 0.001). Presence of PD-1 TILs also correlates significantly with better OS (P = 0.005) and DFS (P = 0) in the human papilloma virus (HPV)-negative cohort. Cox regression multivariate analysis revealed PD-1 TIL expression as an independent prognostic marker for OS (P = 0.004) and DFS (P = 0.001) and T stage was validated as negative prognostic marker for OS (P = 0.011). PD-1-expressing lymphocytes (P = 0.0412) and PD-L1 expression (P = 0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases. CONCLUSIONS: Our results characterise the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers.

ÖGRO survey on radiotherapy capacity in Austria : Status quo and estimation of future demands.

BACKGROUND: A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO). MATERIALS AND METHODS: All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands. RESULTS: For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16-24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5-29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively. CONCLUSION: This ÖGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.

Comparative Analysis of Clinical and Pathological Lymph Node Staging Data in Head and Neck Squamous Cell Carcinoma Patients Treated at the General Hospital Vienna.

BACKGROUND: Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature. PATIENTS AND METHODS: In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus postoperative radiotherapy between 2002 and 2012. For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned data obtained by CT or MRI were available. Overall survival rates were estimated by the Kaplan-Meier method. The Pearson correlation coefficient and Spearman's rank correlation coefficient (non-linear relationship) was calculated. RESULTS: Discrepancies at the level of overall tumour stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumour. At the lymph node level, 11.5% of the patients were downstaged, and 10.3% were upstaged. CONCLUSIONS: The study showed that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

Primary radiotherapy or postoperative radiotherapy in patients with head and neck cancer: Comparative analysis of inflammation-based prognostic scoring systems.

INTRODUCTION: Inflammation-based scoring systems have potential value in evaluating the prognosis of cancer patients; however, detailed comparative analyses in well-characterized head and neck cancer patient collectives are missing. METHODS: We analyzed overall survival (OS) in locally advanced head and neck cancer patients who were treated with curative intent by primary radiotherapy (RT) alone, by RT in combination with cetuximab (RIT) or with cisplatin (RCHT), and by primary surgery followed by postoperative radiotherapy (PORT). The primary RT collective (N = 170) was analyzed separately from the surgery plus RT group (N = 148). OS was estimated using the Kaplan-Meyer method. Cox proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors and the inflammation-based Glasgow Prognostic Score (GPS), the modified GPS (mGPS), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the prognostic index (PI). RESULTS: A prognostic relevance of the scoring systems for OS was observed in the primarily irradiated, but not in the PORT collective. OS was 35.5, 18.8, and 15.4 months, respectively, according to GPS 0, 1, and 2. OS according to mGPS 0-2 was identical. The PLR scoring system was not of prognostic relevance, while OS was 27.3 months in the NLR 0 group and 17.3 months in the NLR 1 group. OS was 35.5 months in PI 0, 16.1 months in PI 1, and 22.6 months in PI 2. CONCLUSION: GPS/mGPS scoring systems are able to discriminate between three risk groups in primarily, but not postoperatively irradiated locally advanced head and neck cancer patients.

Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy.

INTRODUCTION: In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear. METHODS: We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. RESULTS: Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival. CONCLUSION: p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations.

Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy.

RATIONALE: Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome, and limited therapeutic options. Fibroblast growth factors (FGFs) and their receptors are potential targets for cancer therapy, but their significance in mesothelioma has remained largely undefined. OBJECTIVES: To investigate the antimesothelioma potential of FGF receptor 1 (FGFR1) inhibition. METHODS: Expression of FGFs and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate FGFR1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation. MEASUREMENTS AND MAIN RESULTS: FGFR1, FGF2, and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration, and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant-negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation, and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation, mitogenic signaling, and apoptosis induction were observed in vivo. Inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin. CONCLUSIONS: Our data suggest that the malignant phenotype of mesothelioma cells depends on intact FGF signals, which should be considered as therapeutic targets with a promising chemo- and radiosensitizing potential.

Significance of p16 expression in head and neck cancer patients treated with radiotherapy and cetuximab.

BACKGROUND: HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated. MATERIALS AND METHODS: We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan-Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data. RESULTS: Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6% positivity; 92% of all cases), while EGFR was expressed at high levels in all tumor subsites (82%). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80% in p16-positive vs. 33% overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival. CONCLUSION: Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.

Postoperative failure of platelet recovery is an independent risk factor for poor survival in patients with oral and oropharyngeal cancer.

OBJECTIVE: The aim of this study was to evaluate the postoperative platelet count changes in patients with oral and oropharyngeal squamous cell carcinoma undergoing preoperative chemoradiotherapy in order to test the hypothesis that the failure of platelets to recover to normal range within 7 days after surgery represents a significant risk factor for poor survival. MATERIALS AND METHODS: A cohort of 102 patients with primary locally advanced oral and oropharyngeal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery was retrospectively analyzed. For each patient, platelet counts were evaluated prior to neoadjuvant treatment, prior to surgery and throughout postoperative days 1 to 7. The Kaplan-Meier method and Cox regression models were used to assess the impact of platelet count changes on survival. RESULTS: Overall survival rate at 5 years was 28% for patients whose platelets did not recover by day 7, with 52% for patients whose platelets remained within a normal level or recovered to this by day 7 (p = 0.005). In multivariate analysis, failure of platelet recovery by day 7 was independently associated with shorter overall survival (p = 0.03). CONCLUSIONS: We demonstrated that the failure of platelets to recover to normal range by the seventh postoperative day is an independent adverse prognostic factor in patients with oral and oropharyngeal cancer undergoing neoadjuvant treatment and surgery. CLINICAL RELEVANCE: Our results indicate that physicians should pay closer attention to monitoring the postoperative platelet count course, as it may predict the clinical outcome of patients with oral and oropharyngeal cancer.

CD34(+)/CD38(-) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin.

BACKGROUND: CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias. DESIGN AND METHODS: We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined. RESULTS: As assessed by flow cytometry, stem cell-enriched CD34(+)/CD38(-)/CD123(+) leukemic cells expressed significantly higher levels of CD33 compared to normal CD34(+)/CD38(-) stem cells. Moreover, highly enriched leukemic CD34(+)/CD38(-) cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34(+)/CD38(-) cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells. CONCLUSIONS: CD33 is expressed abundantly on immature CD34(+)/CD38(-) stem cells and may serve as a stem cell target in chronic myeloid leukemia.

Basic principles of molecular effects of irradiation.

In order to understand the consequences of radiation a thorough understanding of the radiobiological mechanisms of the molecular up to the clinical level is of importance. Radiobiology therefore combines the basic principles of physics as well as biology and medicine and is concerned with the action of radiation from the subcellular level up to the living organism. Topics of interest and relevance are covered in much more broadness as is possible in the short following article in the literature to which the interested reader is referred to. Classical books in this field were written by Steel et al. (1989) as well as by Hall (1994). Topics usually covered by radiobiological reviews are the classification of different types of radiation, cell cycle dependency of radiation effects, types of radiation damage and cell death, dose response curves, measurement of radiation damage, the oxygen effect, relative biological effectiveness, the influence of dose rate, and several other important research areas. This short overview will concentrate on a subset of radiobiological topics of high importance and relative novelty.

4-({(Z)-5-[(Z)-3-Eth-oxy-4-hy-droxy-benzyl-idene]-3-methyl-4-oxo-1,3-thia-zolidin-2-yl-idene}amino)-benzoic acid dimethyl-formamide monosolvate.

The mol-ecular structure of the title compound, C20H18N2O5S·C3H7NO, represents an essentially planar 5-benzyl-idene-thia-zolidine moiety (r.m.s. deviation from planarity without ring substituents = 0.095 Å) to which the 4-amino-benzoic acid fragment is inclined at 76.23 (1)°. In the crystal, the benzoic acid mol-ecules are arranged in layers parallel to [001] which are built up from inversion dimers held together by head-to-tail phenol-carb-oxy O-H⋯O hydrogen bonds and head-to-tail π-π stacking inter-actions between the 5-benzyl-idene-thia-zolidine moieties (ring centroid distance = 3.579 Å). These layers are separated by the dimethyl-formamide solvent mol-ecules which are firmly anchored via a short O-H⋯O hydrogen bond [O⋯O = 2.5529 (10) Å] donated by the -COOH group.

Incidence of dermatitis in head and neck cancer patients treated with primary radiotherapy and cetuximab.

PURPOSE: To retrospectively assess the incidence of radiation dermatitis in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who received primary radiotherapy in combination with cetuximab in a curative intent. PATIENTS AND METHODS: A total of 112 consecutively treated patients who received cetuximab in combination with radiotherapy at the Departments of Radiotherapy at the Medical University in Vienna and the Hospital Hietzing (Vienna) were analyzed. Radiotherapy was administered either as conventional radiotherapy (70 Gy in 7 weeks) or using a concomitant boost protocol (72 Gy in 6 weeks). The incidence of dermatitis and mucositis within the radiation portals in 103 eligible patients was compared with a historical control group treated at the Medical University of Vienna as well as with published data. RESULTS: The incidence of grade 1/2, 3, and 4 dermatitis was 57%, 29%, and 1% in the radiotherapy plus cetuximab treated collective. The incidence of grade 1/2, 3, and 4 mucositis was 37%, 47%, and 4%, respectively. The incidence of grade 3 dermatitis during concurrent radiotherapy plus cetuximab was 29% in our patient collective. Only one case of grade 4 dermatitis was observed. CONCLUSION: These results do not statistically differ significantly from the incidence reported in the Bonner trial and indicate that cetuximab in combination with radiotherapy is well tolerated.

Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis.

OBJECTIVE: To investigate the mechanisms leading to the influx of inflammatory hematopoietic cells into the synovial membrane and the role of tumor necrosis factor receptor I (TNFRI) and TNFRII in this process in an animal model of rheumatoid arthritis (RA). METHODS: We performed bone marrow transplantations in human TNF-transgenic mice using hematopoietic cells from wild-type, TNFRI(-/-), TNFRII(-/-), and TNFRI/II(-/-) mice as donors and assessed the severity of arthritis histologically. Generation of osteoclasts from the different genotypes was analyzed in vitro and in vivo. Apoptosis was analyzed using annexin V staining as well as TUNEL assays. RESULTS: Despite lacking responsiveness to TNF in their hematopoietic compartment, mice not only developed full-blown erosive arthritis but even showed increased joint destruction when compared with mice with a TNF-responsive hematopoietic compartment. We demonstrated different roles of the 2 different TNFRs in the regulation of these processes. The absence of TNFRI on hematopoietic cells did not affect joint inflammation but markedly attenuated erosive bone destruction via reduced synovial accumulation of osteoclast precursors. In contrast, the absence of TNFRII on hematopoietic cells increased joint inflammation as well as erosive bone destruction via the regulation of osteoclast precursor apoptosis. CONCLUSION: Our findings indicate that selective blockade of TNFRI, leaving the antiinflammatory effects of TNFRII unaltered instead of unselectively blocking TNF, might be advantageous in patients with RA.

Betulinic acid a radiosensitizer in head and neck squamous cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Betulinic acid, a pentacyclic triterpene, is a new cytotoxic compound active on melanoma, neuroblastoma, glioblastoma and head and neck squamous cell carcinoma (HNSCC) cells. In combination with irradiation it has been shown to have an additive effect on growth inhibition in melanoma cells. In this study, the radiosensitizing effect of betulinic acid on sequential irradiation was investigated in HNSCC cell lines. MATERIAL AND METHODS: Two HNSCC cell lines, SCC9 and SCC25, were treated with increasing doses of betulinic acid and sequentially irradiated with a single boost of 4 Gy from a conventional radiation source. The cells were counted, the surviving fraction was determined, and colony-forming assays were performed. RESULTS: It could be shown that betulinic acid alone inhibits cell survival, affects cell survival additively in combination with irradiation and decreases clonogenic survival in both cell lines when applied alone. CONCLUSION: Betulinic acid could be a promising treatment agent in radioresistant head and neck cancer. A combination of betulinic acid with radiotherapy seems to be beneficial.

After injection into the striatum, in vitro-differentiated microglia- and bone marrow-derived dendritic cells can leave the central nervous system via the blood stream.

The prototypic migratory trail of tissue-resident dendritic cells (DCs) is via lymphatic drainage. Since the central nervous system (CNS) lacks classical lymphatic vessels, and antigens and cells injected into both the CNS and cerebrospinal fluid have been found in deep cervical lymph nodes, it was thought that CNS-derived DCs exclusively used the cerebrospinal fluid pathway to exit from tissues. It has become evident, however, that DCs found in peripheral organs can also leave tissues via the blood stream. To study whether DCs derived from microglia and bone marrow can also use this route of emigration from the CNS, we performed a series of experiments in which we injected genetically labeled DCs into the striata of rats. We show here that these cells migrated from the injection site to the perivascular space, integrated into the endothelial lining of the CNS vasculature, and were then present in the lumen of CNS blood vessels days after the injection. Moreover, we also found these cells in both mesenteric lymph nodes and spleens. Hence, microglia- and bone marrow-derived DCs can leave the CNS via the blood stream.

The cyclooxygenase-2 inhibitor nimesulide, a nonsteroidal analgesic, decreases the effect of radiation therapy in head-and-neck cancer cells.

BACKGROUND: No data are available on the effects of the cyclooxygenase-2 (COX-2) inhibitor nimesulide in combination with irradiation on the survival of head-and-neck carcinoma cells. MATERIAL AND METHODS: Two head-and-neck carcinoma cell lines (SCC9 and SCC25) were treated with nimesulide (50-600 microM) and irradiated concomitantly or sequentially. Early effects on cell survival were investigated by counting cell numbers, long-term effects by colony-forming assays. Cell-cycle effects were analyzed 24-72 h after treatment with nimesulide by flow cytometry. RESULTS: Unexpectedly, nimesulide solely inhibited cell proliferation without affecting colony-forming ability. In addition, no evidence for a radiosensitizing effect of nimesulide in short-term assays was seen. Nimesulide alone had no effect on clonogenic survival alone or in combination with radiation. CONCLUSION: Nimesulide differentially affects cell proliferation and clonogenic survival and may decrease the efficacy of radiotherapy. Short-term assays to assess tumor growth may not correctly predict the clinically relevant long-term effect of COX-2 inhibitors.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries.

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Correction: Fibroblast growth factor receptor 4 induced resistance to radiation therapy in colorectal cancer.

[This corrects the article DOI: 10.18632/oncotarget.12099.].