A comparative assessment of the effects of integrin inhibitor cilengitide on primary culture of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines.

BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors, cilengitide is suggested to be one of the most promising inhibitors. However, little is known about the cellular processes induced during cilengitide chemotherapy in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: For the current study, 3 HNSCC cell lines, SCC4, SCC15 and SCC25; and 3 primary culture cells, TU53, TU57, and TU63 were used. CD90, cytokeratin, and vimentin were stained immunohistochemically to identify the biological characteristics of these cell lines and primary culture cells and the cytostatic effect of cilengitide was evaluated. Quantitative polymerase chain reaction (qPCR) arrays were applied to evaluate target protein genes ITGAV, ITGB3, and ITGB5 of integrin αvß3 and αvß5 at respective concentrations of 50 and 100 µM cilengitide for 72 h. RESULTS: Cilengitide has significantly inhibited the proliferation of HNSCC cells in a dose-dependent way. At the same concentration, cilengitide suppressed the proliferation of primary culture cells even more strongly than it did that of cell lines, suggesting that primary culture cells retain more of their internal biological characteristics than do cell lines. qPCR assay detected downregulation of ITGAV, ITGB3, and ITGB5 gene expression after exposure to 50 µM of cilengitide. However, after exposure to 100-µM cilengitide, expression of these genes significantly increased both in cell lines and primary culture cells. CONCLUSIONS: RGD-containing small-molecule synthetic peptides might be considered in tumor chemotherapy in the near future. The different reactions of primary culture cells and cell lines demonstrated that individualized chemotherapy plans may be a feasible option. However, research on the role of cilengitide in HNSCC therapy is still in its early stages, and further investigations are required.

Effects of zoledronate on the radiation-induced collagen breakdown: a prospective randomized clinical trial.

BACKGROUND: A negative side effect of therapeutic irradiation is the radiation-induced bone loss which can lead, in long term, to pathological fractures. Until today, the detailed mechanism is unknown. If osteoclasts would mainly contribute to the pathological bone loss, bisphosphonates could potentially counteract the osteolytic process and possibly help to prevent long-term complications. The aim of this study was to evaluate the effect of zoledronic acid on the early radiation-induced degradation of bone collagen fibrils by monitoring the urinary excretion of hydroxylysylpyridinoline and lysylpyridinoline under radiotherapy. PATIENTS AND METHODS: A total of 40 patients with skeletal metastases were assigned for a local radiotherapy and bisphosphonate treatment. The patients were prospectively randomized into two treatment groups: group A (n = 20) received the first zoledronate administration after and group B (n = 20) prior to the radiotherapy. Urine samples were collected from each patient on the first day, in the middle, and on the last day of the radiation therapy. Measurement of the bone metabolites hydroxylysylpyridinoline and lysylpyridinoline was performed by high-performance liquid chromatography. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: The hydroxylysylpyridinoline and lysylpyridinoline excretion decreased significantly in the combined bisphosphonate and radiotherapy group (p = 0.02, p = 0.08). No significant change of the hydroxylysylpyridinoline and lysylpyridinoline excretion was determined in the patients that received solely irradiation. CONCLUSION: The results indicate the ability of zoledronate to prevent the early radiation-induced bone collagen degradation suggesting that the radiation-induced bone loss is mainly caused by osteoclastic bone resorption rather than by a direct radiation-induced damage.

Trabalho de consenso de força-tarefa da WFSBP sobre marcadores biológicos das demências: contribuição da análise do LCR e do sangue para o diagnóstico precoce e diferencial das demências / Consensus Paper of the WFSBP Task Force on Biological Markers of Dementia: The role of CSF and blood analysis in the early and differential diagnosis of dementiaWorld J Biol Psychiatry

O envelhecimento da população e o aumento da expectativa de vida resultam em um número cada vez maior de pacientes com demência. Os déficits cognitivos podem ser manifestações de uma doença curável do sistema nervoso central (por exemplo, neuroinflamação), como também de uma doença atualmente considerada irreversível, como a doença de Alzheimer (DA). Tendo em vista as novas abordagens terapêuticas para a DA, em que se avalia o potencial modificador da patogenia, torna-se necessário o estabelecimento de um diagnóstico confiável em vida. Embora a análise do líquido cefalorraquidiano (LCR) e do soro seja realização de rotina em doenças neuroinflamatórias, ainda necessita de padronização para ser usada como instrumento auxiliar no diagnóstico clínico da DA. Vários parâmetros relacionados à DA (tau total, formas fosforiladas de tau, peptídeos Aβ, genótipo ApoE, p97 etc.) podem ser determinados no LCR. A combinação de alguns desses parâmetros proporciona sensibilidade e especificidade na faixa de 85 por cento para o diagnóstico da DA, um valor usualmente atribuído a um bom instrumento de diagnóstico. Nesta revisão, são discutidas as publicações mais recentes sobre os marcadores neuroquímicos para o diagnóstico clínico das demências, com ênfase no diagnóstico precoce e diferencial da DA. Discutem-se brevemente as novas perspectivas oferecidas por tecnologias recentes, tais como a FCS (fluorescence correlation spectroscopy) e a técnica de espectrometria de massa pelo método SELDI-TOF (surface enhanced laser desorption/ionization time-of-flight mass spectrometry).

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Aß peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85 percent, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.