Thymosin beta-4 - A potential tool in healing middle ear lesions in adult mammals.

Acute tympanic membrane perforations primarily occur due to injury or infection in humans. In acute cases, nearly 80-94 % of the perforations heal spontaneously. In chronic cases, non-surgical treatment becomes significantly limited, and the perforation can be restored only by myringoplasty. In addition to classical grafts such as the fascia or cartilage, promising results have been reported with various biological materials including silk or acellular collagen. However, despite of all the efforts, healing remains insufficient. Consequentially, a need for substances which actively promote tympanic cell migration and proliferation is deemed essential. In our study, we utilized Thymosin beta-4 (TB4), a 43aa peptide possessing many regenerative properties in various organ systems. Our aim was to reveal the impact of externally administered TB4 regarding impairments of the middle ear, particularly the tympanic membrane. We harvested tympanic membranes from adult mice and treated these with TB4 or PBS on both collagen gel matrixes and in the form of floating, ex vivo explants. Cell migration and proliferation was measured, while immunocytochemical analyses were performed to determine cell type and the nature of the targeted molecules. We discovered the peptide affects the behavior of epidermal and epithelial cells of the tympanic membrane in vitro. Moreover, as our initial results imply, it is not the differentiated, yet most likely the local epidermal progenitor cells which are the primary targets of the molecule. Our present results unveil a new, thus far undiscovered field regarding clinical utilization for TB4 in the future.

Aortabillentyu-beültetés antifoszfolipid szindrómában.

Esetismertetés: Egy 44 éves férfi betegnél endokarditisz talaján kialakult súlyos aortabillentyu-elégtelenség tett szükségessé szívsebészeti beavatkozást. A kevesebb mint egy év alatt bekövetkezett többszöri trombotikus esemény felvetette antifoszfolipid szindróma lehetoségét. A lupus antikoaguláns pozitivitás és az említett klinikai kép ezt igazolta. Megbeszélés: Betegünk fiatal életkora és a biológiai mubillentyu korlátozott élettartama ellenére biológiai mubillentyu beültetése mellett döntöttünk. Választásunkat azzal indokoljuk, hogy tanulmányok bizonyítják antifoszfolipid szindrómás betegeknél a mechanikus mubillentyuvel összefüggésbe hozható thromboembolia viszonylag gyakori elofordulását. A mutétet szövodménymentesen elvégeztük, aktivált parciális thromboplastin idovel kontrollált Na-heparin korai adása mellett állítottuk be az orális antikoaguláns terápiát 3,0 INR célértékkel a mutét utáni ötödik napra. A mutét során eltávolított billentyubol korokozó nem tenyészett ki. A kórszövettani vizsgálat abakteriális endokarditiszt véleményezett, nem kizárva a korábbi fertozést. Biológiai mubillentyu implantáció után három hónapig ajánlott aszpirin vagy K-vitamin antagonista adása, betegünk esetében viszont élethosszig tartó antikoaguláns kezelés szükséges, tekintettel rendszerbetegségére. Következtetés: Halmozódó tromboembóliás események kapcsán gondolni kell antifoszfolipid szindrómára, mely igazolása adott esetben meghatározhatja a választható mubillentyu fajtáját. Az ajánlások legtöbbször csak általánosságban fedik le a ritka társbetegségeket, ezért a kapcsolódó szakirodalom áttekintése is szükséges az optimális, betegre szabott döntéshez.

Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To improve pre- and post-operative diagnosis and prognosis novel molecular markers are desirable. Here we used MALDI imaging mass spectrometry (IMS) and immunohistochemistry (IHC) to seek tumor specific expression of proteins and lipids in HNSCC samples. Among low molecular weight proteins visualized, S100A8 and S100A9 were found to be expressed in the regions of tumor tissue but not in the surrounding healthy stroma of a post-operative microdissected tissue. Marker potential of S100A8 and S100A9 was confirmed by immunohistochemistry of paraffin-embedded pathological samples. Imaging lipids showed a remarkable depletion of lysophosphatidylcholine species LPC[16:0], LPC[18:2] and, in parallel, accumulation of major glycerophospholipid species PE-P[36:4], PC[32:1], PC[34:1] in neoplastic areas. This was confirmed by shotgun lipidomics of dissected healthy and tumor tissue sections. A combination of the negative (LPC[16:0]) and positive (PC[32:1], PC[34:1]) markers was also applicable to uncover tumorous character of a pre-operative biopsy. Furthermore, marker potential of lysophospholipids was supported by elevated expression levels of the lysophospholipid degrading enzyme lysophospholipase A1 (LYPLA1) in the tumor regions of paraffin-embedded HNSCC samples. Finally, experimental evidence of 3D cell spheroid tests showed that LPC[16:0] facilitates HNSCC invasion, implying that HNSCC progression in vivo may be dependent on lysophospholipid supply. Altogether, a series of novel proteins and lipid species were identified by IMS and IHC screening, which may serve as potential molecular markers for tumor diagnosis, prognosis, and may pave the way to better understand HNSCC pathophyisiology.

Urothelial Papilloma of the Urinary Bladder in Children: Report of Two Cases.

Urothelial neoplasms of the bladder (UNB) are considerably rare throughout the pediatric population. UNB develops from the urothelial tissue in the form of a benign disease, generally favoring a successful prognosis in the majority of cases. The authors present the diagnosis and treatment regarding two medical case reports in which urothelial papilloma was diagnosed and effectively treated. Case 1 : A 15-year-old male patient was presented to our clinic complaining of a painless yet distinctive, macroscopic form of hematuria. Following a routine examination, which included ultrasound (US) and intravenous pyelography, the urethrocystoscopy revealed an intravesical solitary lesion positioned in the vicinity of the left ureteral orifice. Additionally, histology confirmed urothelial papilloma. During the follow-up, laboratory, urinary control tests, and US results all proved negative. Case 2 : A 13-year-old male patient was admitted to our clinic and examined, in regard to complaints associated with recurrent abdominal pain. The pathology was discovered incidentally on abdominal US. Preoperative US and magnetic resonance imaging (MRI) studies ensued, resulting in a scheduled MRI, followed by urethrocystoscopy, which confirmed an intravesical solitary lesion positioned near the right ureteral orifice. Histology revealed urothelial papilloma. During the follow-up control cystoscopy, one resection was repeated due to the presence of a residual tumor. Today, 10 years since the presence of uroepithelial papilloma, both patients are asymptomatic and tumor-free. If there is likely suspicion of recurrence, cystoscopy is recommended.

Label-Free Semiquantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics Analysis of Laryngeal/Hypopharyngeal Squamous Cell Carcinoma on Formalin-Fixed, Paraffin-Embedded Tissue Samples - a Pilot Study.

Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aim of this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.

Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer.

The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.

Ganglioneuroma in the papilla of Vater with neurofibromatosis type 1: report of a case.

Ganglioneuromas (GNs) are rare benign tumors and their association with neurofibromatosis type 1 (NF-1) is especially uncommon. We report in this article the case of a young woman, subjected to diagnostic work-up because of abdominal pain. Endoscopy and histology revealed not only a GN in the papilla of Vater, but also NF-1. Because of the size and macroscopic features of the lesion, we performed pancreatoduodenectomy, from which she recovered uneventfully. Histological examination of the resected tumor confirmed a diagnosis of GN.