HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. METHODS: 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. RESULTS: HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05). CONCLUSION: HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy

Genome-wide Investigation of multifocal and unifocal prostate cancer-are they Genetically different?

Prostate cancer is widely observed to be biologically heterogeneous. Its heterogeneity is manifested histologically as multifocal prostate cancer, which is observed more frequently than unifocal prostate cancer. The clinical and prognostic significance of either focal cancer type is not fu

The use of tumour necrosis factor alpha-blockers in daily routine. An Austrian consensus project

To define relevant disease parameters and their respective limits indicating the initiation of TNF-α-blockers in individual patients. Subsequently, to analyze retrospectively patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), who started TNF-α inhibition in 2006. Points to consider, regarded relevant for individual treatment decisions as well as their assessment methods, were ascertained by experts’ consensus applying the Delphi technique. Subsequently, these parameters’ thresholds with respect to the initiation of a TNF-α-blocker were identified. Thereafter, the rheumatologists representing 12 centres all over Austria agreed to retrospectively analyze their patients started on a TNF-α-blocker in 2006. Experts’ opinion regarding disease parameters relevant to initiate TNF-α-blockers in RA patients only slightly differed from those applied in clinical trials, but the parameters’ threshold values were considerably lower. For PsA patients, some differences and for AS patients, considerable differences between experts’ opinion and clinical studies appeared, which held also true for decisive parameters’ means and thresholds. Six hundred and fifty patients, started on TNF-blockers in 2006, could be analyzed retrospectively, 408 RA patients (53.3 years mean, 340 females), 93 PsA patients (48.9 years mean, 59 males) and 149 AS patients AS (42.2 years mean, 108 males), representing approximately 25% of all Austrian patients initiated on a TNF-blocker in this respective year. Far more individualized, patient-oriented treatment approaches, at least in part, are applied in daily routine compared with those derived from clinical trials or recommendations from investigative rheumatologists

Molecular targeted therapies for breast cancer treatment

Targeting the oestrogen receptor, HER2 (human epidermal growth factor receptor 2) and vascular endothelial growth factor has markedly improved breast cancer therapy. New targeted therapeutic approaches to induction of apoptosis or inhibition of anti-apoptosis, cell cycle progression, signal transduction and angiogenesis are described. The molecular pathways and their inhibitory or repair mechanisms are discussed in the preclinical and clinical settings

Complex movement disorder in a patient with heterozygous YY1 mutation (Gabriele-de Vries syndrome)

YY1 mutations cause Gabriele-de Vries syndrome, a recently described condition involving cognitive impairment, facial dysmorphism and intrauterine growth restriction. Movement disorders were reported in 5/10 cases of the original series, but no detailed description was provided. Here we present a 21-year-old woman with a mild intellectual deficit, facial dysmorphism and a complex movement disorder including an action tremor, cerebellar ataxia, dystonia, and partial ocular apraxia as the presenting and most striking feature. Whole-exome sequencing revealed a novel heterozygous de novo mutation in YY1 [NM: 003403.4 (YY1): c.907 T > C; p.(Cys303Arg)], classified as pathogenic according to the ACMG guidelines

The Heavenly Sanctuary/Temple Motif in the Hebrew Bible : Function and Relationship to the Earthly Counterparts

The present dissertation investigates the function of the heavenly sanctuary/temple and its relationship to the earthly counterparts, as reflected in forty-three passages of Hebrew Bible. Following an introductory chapter, the second chapter of this dissertation is devoted to a survey of the heavenly sanctuary/temple motif in the ANE literature, as represented by Sumerian, Akkadian, Hittite, Ugaritic, and Egyptian texts. The investigation of these texts reveals that the heavenly sanctuary/temple motif was part of the worldview of the ANE, where the heavenly sanctuary was not only assumed as existing in heaven, but also as functioning in close relationship to the earthly counterparts. Chapters 3, 4, and 5 are devoted to the exegesis of heavenly sanctuary/temple passages in the Hebrew Scriptures, according to the canonical divisions of the Hebrew Bible (namely Torah, Prophets, and Writings). This investigation reveals the pervasive presence of the heavenly sanctuary/temple motif in the Hebrew Bible and provides a broad delineation of its function and relationship to the earthly counterparts. It has been found that the heavenly sanctuary temple functions as a place of divine activities where YHWH supervises the cosmos, performs acts of judgment (sometimes conceived as a two-stage activity in which the execution of the sentence was preceded by an investigative phase), hears the prayers of the needy, and bestows atonement and forgiveness upon the sinners. The perception also emerged of the heavenly sanctuary/temple as a place of worship, a meeting place for the heavenly council, and an object of attack by anti-YHWH forces, thus playing a pivotal role in the cosmic battle between good and evil. In terms of its relationship to the earthly counterparts, it becomes apparent that the heavenly sanctuary/temple was understood to operate in structural and functional correspondence to the earthly counterparts. Moreover, some texts reveal a dynamic interaction between heavenly and earthly sanctuaries/temples, inasmuch as the activities of one could affect the other. Chapter 6 presents a theological synthesis of the heavenly sanctuary/temple motif based on the previous chapters. Some consideration is given to the similarities and differences between the heavenly sanctuary/temple motif as found in the Hebrew Bible and in its ANE background. Next, attention is devoted to some theological implications of the heavenly sanctuary/temple motif for the notions of judgment, cosmic battle, and covenant. To conclude, the Hebrew Bible conceives of the heavenly sanctuary/temple in functional and structural correspondence with its earthly counterpart with both sanctuaries/temples operating in dynamic interaction