Nebennieren-Inzidentalome werden durch den zunehmenden Einsatz von bildgebenden Methoden immer häufiger zufällig entdeckt. Hierbei liegen vorrangig klinisch unauffällige Nicht-Aldosteron-produzierende adrenokortikale Adenome (NAPACA) vor, wobei Nicht-funktionelle Adenome (NFA) von Tumoren mit (möglicher) autonomen Cortisol-Sekretion (MACS und ACS) zu differenzieren sind. Der Verlauf und die Prognose dieser Patienten werden teilweise noch kontrovers diskutiert. Die wesentlichen Fragestellungen dieser Arbeit lauteten, welche Dynamik Nebennieren-Inzidentalome (und hierbei insbesondere die NAPACA) hinsichtlich Hormonsekretion und Malignitätspotential aufweisen und welchen Einfluss sie auf das Gesamtüberleben der Betroffenen ausüben. In dieser Studie wurde hierfür das Patientenkollektiv des Universitätsklinikums Würzburg zwischen 1998 und 2017 retrospektiv untersucht. Die Zuordnung zu Entitäten und die Interpretation der Daten erfolgte dabei anhand der Empfehlungen der aktuellen Europäischen Leitlinie zum Management von Nebennieren-Inzidentalomen. Für diese Arbeit wurden 357 Patienten mit einem Nebennieren-Inzidentalom identifiziert, von denen 263 (73,7 %) der NAPACA-Gruppe zuzuordnen waren. Im Verlauf kam es bei 39 (10,9 %) der Patienten zu relevanten Veränderungen der endokrinen Aktivität und bei 4 (1,1 %) auch der Dignität, wodurch die Zuordnung zu einer anderen Tumorentität notwendig wurde. In den Mortalitätsanalysen stellten Hormonaktivität und Malignität relevante prognostische Einflüsse bei Patienten mit Nebennieren-Inzidentalom dar. Speziell Patienten mit MACS und ACS wiesen eine höhere Gesamtmortalität auf als solche mit NFA, wobei das Serumcortisol im Dexamethason-Suppressionstest für die multivariaten Cox-Regressionsanalysen als kontinuierliche und nicht kategoriale Variable betrachtet wurde. NAPACA-Patienten starben vorrangig an malignen, kardiovaskulären und infektiösen Ursachen. Zusammenfassend weisen Patienten mit Nebennieren-Inzidentalom im Allgemeinen und mit NAPACA im Speziellen im Verlauf eine geringe endokrinologische und maligne Dynamik auf. Ihr Gesamtüberleben wird maßgeblich von Hormonaktivität und Dignität bzw. von der Höhe des Serumcortisols im Dexamethason-Hemmtest beeinflusst. / Incidental discoveries of adrenal tumors are increasing due to the rising use of imaging. Clinically inapparent non-aldosterone-producing adrenocortical adenomas (NAPACA) are most common, although non-functional adenomas (NFA) should be differentiated from tumors with (possible) autonomous cortisol secretion (MACS and ACS). To what extent the prognosis of patients with adrenal incidentaloma is affected is still a controversial matter. The main questions addressed were the dynamics of adrenal incidentalomas (and in particular NAPACA) with regard to hormone secretion and malignancy potential and what influence they have on the overall survival of those affected. In this study, patients of the University Hospital of Würzburg were retrospectively examined between 1998 and 2017. The workup and interpretation of data was based on the recommendations of the current European guidelines for the management of adrenal incidentalomas. For this work, 357 patients with an adrenal incidentaloma were identified, of which 263 (73.7%) were assigned to the NAPACA group. During the study, relevant changes in endocrine activity occurred in 39 (10.9%) patients and in dignity in 4 (1.1%) patients, which made assignment to a different tumor entity necessary. In the mortality analyses, hormone activity and malignancy were relevant prognostic influences in patients with adrenal incidentaloma. Patients with MACS and ACS in particular had a higher overall mortality than those with NFA, when the serum cortisol in the dexamethasone suppression test was examined as a continuous variable in the multivariate Cox regression analysis. NAPACA patients died primarily from malignant, cardiovascular, and infectious causes. In summary, patients with adrenal incidentaloma in general and with NAPACA in particular show little endocrinological and malignant potentials over the course of the disease. The overall survival is significantly influenced by hormone activity and malignancy or in NAPACA by the level of serum cortisol in the dexamethasone suppression test.

München, Techn. Universiẗat, Diss., 2007.

BALB/c nude mice 6 weeks old were inoculated with glioma C6 cell-line and the efficacy of the different amount of Etanidazole-discs and Taxol-microspheres was investigated. Poly (D,L-lactic-co-glycolic acid) (PLGA) was used as the main encapsulating polymer and polyethylene glycol was added to increase the porosity. The 1% drug loading microspheres of each drug were produced by spray drying and the discs were obtained by compressing the Etanidazole-microspheres. Intra-tumoral injection followed by irradiation resulted in high systemic dosage and thus systemic toxicity. Tumors grown for 6 days, 9 days and 16 days were implanted with 0.5 mg or 1.0 mg or 1.5 mg of the drug. A radiation dosage of 2 Gy each time for a number of times was given for animals implanted with Etanidazole and no irradiation was given for animals implanted with Taxol. Increasing the number of doses clearly decreased the rate of tumor growth. The increase in the amount of drug on smaller sized tumors controlled the tumor better and there was agglomeration of the microspheres resulting in deviation of release profile of the drug as compared to the in vitro studies. It was observed that 1.0 mg of Taxol given to a tumor grown for 6 days was able to suppress the tumor for a total period of approximately two months and no tumor resurrection was observed during the second month. / Singapore-MIT Alliance (SMA)

The failure of the immune system to provide efficient protection against tumour cells has been considered as a major issue in immunology. It is now well established that inadequate function of the host immune system is one of the main mechanisms by which tumours escape from immune control contributing to the limited success of cancer immunotherapy. Several cell populations have been described which display immunosuppressive properties and may impede tumor-specific immunity. Among them, GR1+CD11b+ immature myeloid suppressor cells and CD4+CD25+ regulatory T cells seem to play an important role. These cells accumulate in the spleens of tumour bearing mice and patients with cancer and contribute to immunosuppression by inhibiting the function of CD8+ T cells and/or by promoting tumour angiogenesis. The aim of our work was to define the mechanisms by which a single dose of cyclophosphamide (CTX), a chemical agent commonly used in chemotherapy treatment, induces the rejection of established P815 mastocytoma. Our data show that CTX treatment leads to the selective loss of GR1medCD11b+ splenic myeloid cell producing TGF-â, a cytokine which is known to suppress antitumoral response. Furthermore, injection of CTX causes a decrease in the number of naturally occurring regulatory T cells (CD4+CD25+Foxp3+) in the spleen and the tumor. Finally, CTX treatment induces the differentiation of GR1highCD11b+ splenic myeloid cells into mature GR1highCD11b+CD11c+ (possibly dendritic cells?) which express high levels of CD11c, MHC class II and CD86 molecules. Of note, these cells are mainly detected in tumour necrosis areas. Collectively, these results suggest that CTX prevents suppressive mechanisms and induces a population of CD11c+ myeloid cells which may present tumor antigens and activate T lymphocytes, an hypothesis in line with the requirement for CD4+ cells in CTX-induced long term resistance.

Despite the clonal origins of tumors, the majority of neoplasms are composed of a heterogeneous population of cells. The origins of this phenotype these cells have the potential to get can be associated with cancer stem cells or tumor initiating cells have the potential to self-renew and to differentiate giving rise to all cell types compromising a heterogeneous malignancy. These cells are clinically important as they preferentially give rise to tumors and are therefore hypothesized to account for the longevity and recurrence of neoplastic lesions. Cancer stem cells have been identified from a broad range of hematopoietic, neural and epithelia tumors; however, their function in mesenchymal neoplasms is less well defined. Using the side population assay, we identified a subpopulation of cells within mesenchymal neoplasms, referred to as side population cells, which are enhanced for tumor initiating potential. Importantly, we show a correlation between the percentage of side population cells and tumor grade suggesting clinical prognostic value as the proportion of side population cells may be a predictor of patient outcome. Interestingly side population cells show distinct molecular features when compared to non-side population cells and manipulation of these molecular mechanisms reduces the ability of side population cells to initiate tumor formation in osteosarcoma cell lines. In conjunction with these experiments, we also sought to determine the cellular origins of the mesenchymal neoplasm, aggressive fibromatosis. Using mouse models we show the influence of a mesenchymal precursor cells in the development of this malignancy. These results identify important biological features of mesenchymal neoplasms from which the development of targeted treatment strategies can begin.

No description available.

Despite the clonal origins of tumors, the majority of neoplasms are composed of a heterogeneous population of cells. The origins of this phenotype these cells have the potential to get can be associated with cancer stem cells or tumor initiating cells have the potential to self-renew and to differentiate giving rise to all cell types compromising a heterogeneous malignancy. These cells are clinically important as they preferentially give rise to tumors and are therefore hypothesized to account for the longevity and recurrence of neoplastic lesions. Cancer stem cells have been identified from a broad range of hematopoietic, neural and epithelia tumors; however, their function in mesenchymal neoplasms is less well defined. Using the side population assay, we identified a subpopulation of cells within mesenchymal neoplasms, referred to as side population cells, which are enhanced for tumor initiating potential. Importantly, we show a correlation between the percentage of side population cells and tumor grade suggesting clinical prognostic value as the proportion of side population cells may be a predictor of patient outcome. Interestingly side population cells show distinct molecular features when compared to non-side population cells and manipulation of these molecular mechanisms reduces the ability of side population cells to initiate tumor formation in osteosarcoma cell lines. In conjunction with these experiments, we also sought to determine the cellular origins of the mesenchymal neoplasm, aggressive fibromatosis. Using mouse models we show the influence of a mesenchymal precursor cells in the development of this malignancy. These results identify important biological features of mesenchymal neoplasms from which the development of targeted treatment strategies can begin.

Despite that most vestibular schwannomas are successfully treated with radiotherapy, current follow-up protocols entail years of serial magnetic resonance imaging (MRI) scans to ensure cessation of growth. This pilot study sought to identify early predictors of radiation treatment response using a non-invasive multi-modality imaging approach. We hypothesized that by combining information acquired from dynamic contrast-enhanced MRI (DCE-MRI), diffusion tensor imaging (DTI), and L-¹¹C-methionine positron emission tomography (MET-PET) treatment response could be identified sooner than the current several year waiting period. This thesis presents the baseline MRI and MET-PET results of the pilot study acquired to-date with follow-up data to be acquired in the next six months. Baseline results suggest that DTI and DCE-MRI yield information that may be useful in identifying the response of vestibular schwannomas to radiotherapy. In particular, vestibular schwannomas display elevated mean diffusion coefficients relative to the contra-lateral cerebellum. Also, the novel use of arterial input functions derived from the anterior inferior cerebellar arteries has led to the successful implementation of DCE-MRI pharmaco-kinetic models which may be used to quantitatively monitor tumor response to radiotherapy. Furthermore, MET-PET has shown promise as a tool for evaluating response as all tumors exhibited enhancement under this modality as compared to the contra-lateral side of the brain. Single-voxel spectroscopy with 3T MRI has proven to be a poor technique with which to examine vestibular schwannomas since only two of eight spectra were acquired successfully. All of the techniques that have shown promise as investigatory tools of tumor response can potentially be implemented clinically in the near future.

Cancer has become the major factor causing death in Taiwan. Although brain tumor take a few ratio in cancer, the current therapy shown not effect well. In previous studies, EGCG will promote cancer cells to go apoptosis after treatment with EGCG. But the mechanism in brain tumor is unknown. So, we use EGCG from green tea extract to investigate cell death of human brain tumor cell lines GBM8401, U87MG and U251. The metabolic rates of GBM8401, U87 and U251 are decrease with EGCG treatment, and it is significant in GBM8401. We also examine some genes and proteins related apoptosis by RT-PCR and Western blotting. The accumulation of p21, p27 and p53 are increasing with concentration and time course treatments. EGCG can inhibit the ability of brain tumor to form foci in anchorage-independent growth assay. Our data show that EGCG can inhibit brain tumor cell lines GBM8401, U87 and U251. It is validated that EGCG has the potential of cancer therapy and prevention.

No description available.