A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC

Proteogenomic analysis of Candida glabrata using high resolution mass spectrometry.

Item does not contain fulltextCandida glabrata is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of C. glabrata using high resolution Fourier transform mass spectrometry with MS resolution of 60,000 and MS/MS resolution of 7500. On the basis of 32,453 unique peptides identified from 118,815 peptide-spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the C. glabrata genome. Further, searching the tandem mass spectra against a six frame translated genome database of C. glabrata resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts

Gene Expression Profiling of Gastric Cancer

Stress urinary incontinence (SUI) is the most observed type of urinary incontinence and is defined as the loss of urine following a rise in abdominal pressure. The TVT (Tension-free Vaginal Tape), a mid-urethral sling (MUS), was introduced in 1996 and soon became the gold standard in the surgical treatment of SUI. Over the last decade, numerous MUS devices have been introduced but only some were able to achieve similar results in comparison to the original TVT. The main question of this thesis is whether slings, old and new, for either male and female, can live up to the expectations of both patients and physicians by being both safe and effective in curing urinary incontinence. Secondly, the question is raised whether sling surgery is anatomically safe with regard to those nervous systems which are essential for the sexual function or may actually be responsible for iatrogenic neurological damage during placement. In this thesis we conclude that many slings were, or still are, freely available on the market without any proper pre-market research. Moreover sling surgery can have serious negative side-effects on sexual function that should be a standard part of the informed consent provided when opting for surgery.</p

Extraterrestrial gynecology: could spaceflight increase the risk of developing cancer in female astronauts? An updated review

Outer space is an extremely hostile environment for human life, with ionizing radiation from galactic cosmic rays and microgravity posing the most significant hazards to the health of astronauts. Spaceflight has also been shown to have an impact on established cancer hallmarks, possibly increasing carcinogenic risk. Terrestrially, women have a higher incidence of radiation-induced cancers, largely driven by lung, thyroid, breast, and ovarian cancers, and therefore, historically, they have been permitted to spend significantly less time in space than men. In the present review, we focus on the effects of microgravity and radiation on the female reproductive system, particularly gynecological cancer. The aim is to provide a summary of the research that has been carried out related to the risk of gynecological cancer, highlighting what further studies are needed to pave the way for safer exploration class missions, as well as postflight screening and management of women astronauts following long-duration spaceflight

Gene Expression Profiling of Gastric Cancer

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