PIK3CA, which encodes the catalytic subunit, p110alpha, of phosphatidylinositol 3-kinase (PI3K), is implicated in the development and progression of numerous neoplasias including head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the occurrence of PIK3CA hot-spot mutations in exons 9 and 20, the genomic gain and amplification of PIK3CA, the expression of PIK3CA mRNA and the p110α protein, as well as the expression of phosphorylated-Akt (pAkt) in 33 cases of HNSCC and compared the results with the clinicopathological data. No non-synonymous mutations were detected. PIK3CA copy number gain and amplification were found in 36.4 and 9% of the cases, respectively, whereas mRNA overexpression was observed in 48.5% of the cases. No correlations could be stated between DNA gain, DNA amplification and mRNA expression, either between DNA or mRNA status and p110α expression. Direct associations were found between PIK3CA gain and lymph node metastases (p=0.025) and between mRNA expression and tumour stage (p=0.015). A strong correlation was detected between p110α and pAkt expression (p<0.001). Concluding, PIK3CA could be an oncogene implicated in HNSCC development. However, our data suggest that amplifications or mutations of this gene seldom occur in HNSCC and that epigenetic events can play an important role in advanced tumour stages.
The general human RNA polymerase III transcription factor (TF) IIIC1 has hitherto been ill defined with respect to the polypeptides required for reconstitution of its activity. Here we identify Homo sapiens TFIIIB؆ (HsBdp1) as an essential component of hTFIIIC1 and hT-FIIIC1-like activities. Several forms of HsBdp1 are described. The 250-kDa form of HsBdp1, also designated the "transcription factor-like nuclear regulator," strictly co-eluted with TFIIIC1 activity over multiple chromatographic purification steps as revealed by Western blot with anti-HsBdp1 antibodies and by MALDI-TOF analysis. In addition, TFIIIC1 activity could be depleted from partially purified fractions with antiHsBdp1 antibodies but not with control antibodies. Moreover, highly purified recombinant HsBdp1 could replace TFIIIC1 activity in reconstituted transcription of the VAI gene in vitro. Furthermore, smaller proteins of ϳ90 -150 kDa that were recognized by anti-HsBdp1 antibodies co-eluted with TFIIIC1-like activity. Finally, cytoplasmic extracts from differentiated mouse F9 fibroblast cells that lacked TFIIIC1 activity could be made competent for transcription of the VA1 gene by the addition of TFIIIC1, TFIIIC1-like, or recombinant HsBdp1. These results suggest that HsBdp1 proteins represent essential components of TFIIIC1 and TFIIIC1-like activities.RNA polymerase III transcribes genes encoding small, untranslated RNAs including tRNA, 5 S rRNA, and U6 small nuclear RNA genes (reviewed in Ref. 1). In the yeast Saccharomyces cerevisiae, genes transcribed by RNA polymerase III are governed by promoter elements comprised of A and C boxes (type 1) or A and B boxes (type 2) that are located downstream of the transcription initiation site. Two transcription factors (TF), 1 TFIIIB and TFIIIC, are necessary and sufficient for the transcription of type 2 genes (tRNA), whereas transcription of the type 1 5 S rRNA gene requires, in addition, TFIIIA. S. cerevisiae (Sc) TFIIIC is a stable complex of six polypeptides, whereas ScTFIIIB consists of a less stable association of three components, namely the ScTBP, ScBrf1, and ScBdp1 proteins (reviewed in Refs.
In a retrospective study, the results from 786 samples of alleged sexual assaults during a 5-year period were evaluated. Of the samples, 758 were from female victims and 28 were from male victims. The material examined during this 5-year period consisted of 561 cotton swabs with swabs taken from the genitals, mouth, anus, or skin surface. In addition, textile products were examined 191 times, paper products 23 times, and other evidentiary materials 11 times. The acid phosphatase (acP) test was performed as a preliminary test for all samples, followed by microscopy after Baecchi staining. DNA analysis was performed on 74 samples following individual court orders. The retrospectively evaluated results from this period indicate that additional tests for the detection of sperm on textiles and paper products are dispensable after a negative acP test. This is different for genital swabs, since sperm could be found microscopically in 3% of cases with a negative acP test, and DNA analysis was also successful. However, an individual investigative strategy has to be determined for each case, as, depending on the structure of the case, the evidence of male DNA on a female victim, or on her clothes, for instance, can also have evidentiary value without microscopic proof for sperm.
A 23-year-old male patient presented with reduced visual acuity of the right eye, along with halos and starbursts in both eyes after a one-stage tissue-saving treatment, a combination of myopic photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). After an extensive preliminary examination and analysis of the examination results, aberration-free LASIK retreatment for reducing astigmatism and enlargement of the optical zone with an excimer laser was performed on the right eye. The visual performance and the subjectively perceived optical quality improved postoperatively.
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