Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Although CRC has been comprehensively characterized at the molecular level, the tumor heterogeneity hinders the identification of reliable diagnostic, prognostic and predictive biomarkers. Molecular stratification of CRC is based on prevalent gene mutations and transcription profiles but its significance for clinical practice remains obscure. Indeed, activating mutations in the genes KRAS, NRAS and BRAF are the only predictive biomarkers for anti-EGFR antibody therapy routinely tested the clinic for advanced stages of CRC. Gene expression signatures are important for clarifying the molecular mechanisms of CRC development and progression, but only two such tests for predicting recurrence risk are commercially available. The aim of our study was to propose a diagnostic approach based on mutation and gene expression analysis that can be routinely applied in the clinic for defining the most appropriate treatment strategy for each patient. We used qPCR to determine the presence of KRAS mutations and measure the transcription levels of a panel of 26 genes in 24 CRC patients. Statistical analyses were applied to check for associations between clinico-pathological and molecular parameters. Our results reveal novel data concerning CRC carcinogenesis: almost universal downregulation of EGFR; differential role of the pro-inflammatory cytokines TNF-α and IL-6; overexpression of the vitamin B12 transporter transcobalamin 1; tumor-suppressor function of SETD2, CA7 and GUCA2B. The practical application of these findings has yet to be clarified.
High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.
INTRODUCTION: YKL-40 is a glycoprotein believed potentially to be a marker of various pathological processes. High levels of YKL-40 have been found in cancer and chronic infl ammatory diseases. The function of the glycoprotein is not completely known yet. A possible involvement in angiogenesis and tumor aggressiveness is supposed. Lysosome-associated membrane glycoproteins (LAMP) 1 and 2 are highly conserved proteins with still undefi ned biological functions. There is evidence that they are implicated in autophagy, angiogenesis and tissue remodeling. AIM: The aim of the present study was to investigate the potential relationship between the tissue expression of YKL-40, LAMP-1 and LAMP-2 in glial tumors. MATERIAL AND METHODS: LAMPs and YKL-40 expression was determined by immunohistochemistry in 36 glial tumors. A morphometric analysis of the intensity of tissue expression was performed with the Quick-photo Micro 2.3. system. Area (μm), perimeter (μm), and expression level (%) of the three glycoproteins were calculated. RESULTS: LAMPs were found on cell membranes of glial and endothelial cells, while YKL-40 was detected in the cytoplasm of these cells. Intensive immunohistochemical reaction was present in tumor cells. LAMP-2 showed a more intensive staining compared to LAMP-1. CONCLUSION: We present the fi rst comparative study of YKL-40 and LAMPs in astroglial tumors. The relationship between the expression of the three glycoconjugates indicates a possible participation in the processes of angiogenesis and tissue remodeling during tumor development
INTRODUCTION:Recently, researchers have been considering as adverse prognostic factors in primary glioblastomas not only clinical indicators but also various cellular, genetic and immunological markers. The aim of the present article was to report a case of primary glioblastoma multiforme with poor survival in a patient after surgical intervention, and to determine the unfavorable prognostic markers. CASE REPORT: We present a 71-year-old man with histologically verifi ed glioblastoma multiforme and a postoperative survival of 48 days. The patient did not receive any radiotherapy and adjuvant therapy with temozolomide because of the short survival. Serum and transcription levels of TNF-α, CD44, YKL-40 and IL-6 were determined by molecular-biological and immunological analyses. We found very high transcription levels of the genes CD44, YKL-40 and IL-6, increased gene expression of TNF-α, and elevated serum concentrations of TNF-α, YKL-40 and IL-6 and reduced serum concentration of CD44. CONCLUSION: Molecular-biological and immunological analyses support the hypothesis that glioblastoma multiforme is presented by a heterogeneous group of glial tumors with different clinical course and prognosis. The high expression levels of TNF-α, CD44, YKL-40, and IL-6 indicate that the tumor can be categorized as mesenchymal subtype of glioblastoma multiforme, which accounts for the rapid clinical course and lethal outcome of the condition. РЕЗЮМЕ ВВЕДЕНИЕ: В качестве неблагоприятных прогностических факторов при первичных глиобластомах в последнее время обсуждаются не только клинические показатели, но и различные клеточные, генетические и иммунологические маркеры. ЦЕЛЬ: Работа ставит себе целью анализировать случай с первичной мультиформенной глиобластомой и краткой выживаемостью после оперативной интер-венции, а также и определить неблагоприятные прогностические маркеры. ПРЕДСТАВЛЕНИЕ СЛУЧАЯ: Авторы представляют случай 71-оголетнего мужчины с доказанной мультиформенной глиобластомой и постоперативной выживаемостью в 48 дней. Из-за непродолжительной выживаемости пациент не подвергнут телегамматерапии и адювантной терапии Темозоломид-ом. С помощью молекулярно-биологических и иммунологических анализов определены транскрипционные и сывороточные уровни TNF-α, IL-6, YKL-40 и CD44. Устанавливаются экстремно высокие транскрипционные уровни генов CD44, IL-6 и YKL-40, увеличенная экспрессия TNF-α, сопровожденные повышенной сывороточной концентрацией IL-6, TNF-α и YKL-40 и пониженной сывороточной концентрацией CD44. ЗАКЛЮЧЕНИЕ: Молекулярно-биологический и иммунологический анализы подкрепляют тезу, что мультиформенная глиобластома представлена гетерогенной группой глиальных опухолей различного клинического хода и прогноза. Высокие экспрессионные уровни CD44, TNF-α, IL-6 и YKL-40 являются индикацией субтипизирования опухоли как мезенхимальная мультиформенная глиобластома и вероятно определяет быстрый клинический ход и летальный исход.Ключевые слова: мультиформенная глиобластома, генная экспрессия, проинфляматорные цитокины, YKL-40, CD44 Fol...
We report a case of 56-year-old patient suffering from myxopapillary ependymoma of filum terminale at the level of the fifth lumbar vertebra. The patient presented with progressive complaints of permanent pain in the anal and sacral region with duration of 8 months. When sneezing or attempting to do brisk movements, the pain irradiated to the posterior surface of the right thigh. Vertebral syndrome was absent. Neurological examination demonstrated no other abnormalities. Magnetic-resonance imaging showed intradural tumor of cauda equina at the level of the fifth lumbar vertebra. The present article discusses the role of MRI in the diagnosis of clinical cases presenting with atypical lumboradiculalgia. We have put an emphasis on the early diagnosis of myxopapillary ependymoma of filum terminale which has an impact on the surgical strategy and postoperative outcome.
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