Biomolecular Markers in Cancer of the Tongue

The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis

Carcinosarcoma of the colon: report of a case with morphological, ultrastructural and molecular analysis

BACKGROUND: Carcinosarcoma of the colon is a rare histopathological entity with uncertain histogenesis, that shows both epithelial and mesenchymal malignant differentiation. Carcinosarcoma rarely affects the gastrointestinal tract and only few cases are reported in the colon. Herein we describe a carcinosarcoma of the ascending colon, with morphological, ultrastructural and molecular analysis. CASE PRESENTATION: An 81-year-old man was hospitalised for asthenia, weight loss and iron-deficiency anaemia. The patient underwent colonoscopy and adenocarcinoma was diagnosed by endoscopic biopsy. A right hemicolectomy was performed and, during surgical operation, liver metastases were detected. Histological examination of the surgical specimen revealed areas of both carcinomatous and sarcomatous differentiation, completely separated by fibrous septae. The sarcomatous component exhibited areas of smooth muscle and osteoblastic differentiation, with focal osteoid material deposition. Molecular analysis conducted separately on the epithelial and mesenchymal components revealed the same p53 gene mutation (R282W in exon 8) and identical polymorphisms in p53 exon 4, in EGFR exons 20 and 21, and in c-kit exon 17. Microsatellite markers analysis revealed a common loss of heterozygosis on 18q. Overall, the data are consistent with a common origin of the two tumor components. The patient was treated with 8 cycles of oral capecitabine (1250 mg/m(2 )twice a day for 14 days repeated every 28 days) and two years after surgery is alive with liver metastases. CONCLUSION: Carcinosarcoma of the colon is a rare tumour with both epithelial and sarcomatous components. Molecular analysis of the current case suggests the histogenesis from a common cell progenitor

Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine tumor: a case report with review of the literature

ABSTRACT: Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs. The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies. Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment. Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far. We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967

Implementation of an automated inclusion system for the histological analysis of murine tissue samples: A feasibility study in DSS-induced chronic colitis:

Animal models are powerful tools to expand our understanding of human diseases. Histopathological evaluation of murine experimental models is often required to support further research; thus, a more rigorous evaluation of murine histological samples is strongly advocated. Indeed, the overall quality of tissue sections is critical to draw reliable and accurate conclusions. As several methodological variables may reduce the reliability of the pathological analysis, a standardization of the procedural steps required for the processing of histological murine tissues is advisable. Here, we describe a method to standardize the technical procedure from the initial preparation to the paraffin embedding of murine samples. Specifically, we have implemented an automated inclusion system, that is, the SAKURA Tissue-Tek inclusion instrument, which is routinely used for paraffin inclusion of human samples, to process murine specimens of intestinal inflammation. Colitis severity was assessed in chronically Dextran Sodium Sulphate (DSS)–treated mice by cytofluorimetric analysis of colonic cellular infiltrates, expression of inflammatory genes and histopathological analysis of tissue samples, comparing manual and automated tissue preparation systems. We here conclude that implementation of this technique can significantly increase the quality and the reliability of histopathological examination of murine tissues

A neuronal network of mitochondrial dynamics regulates metastasis.

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater membrane dynamics and heightened cell invasion. Therefore, a SNPH network regulates metastatic competence and may provide a therapeutic target in cancer

Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury

Background and objectives: significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts. Design and methods: ten donor and ten recipient inbred isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by placing a frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze-thaw injury technique). BMMNCs were purified and labeled with a red fluorescent cell dye. Seven days after the injury about 15-25x10(6) cells were infused through the femoral vein of recipient rats. Seven days after the infusion, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. RESULTS: Labeled cells were found only in the injured area of the heart and not in the normal tissue, and a limited number of cells were identified in the spleen of all the animals. Most of the labeled cells in the infarcted area were Thy-1(+) and some were CD34(+). Interpretation and conclusions: our data suggest that peripherally injected BMMNCs can traffic through the circulation to the site of damage; we hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells

Tumor size, stage and grade alterations of urinary peptidome in RCC

Background: Several promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data. Methods: A proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC-ESI-MS/MS. Results: Fifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified. Conclusions: We identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients

Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile

<p>Abstract</p> <p>Background</p> <p>Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.</p> <p>Results</p> <p>We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.</p> <p>Conclusion</p> <p>By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.</p

From EHR to EDC - The Experience at the Policlinico Hospital in Milan.

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Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the stemness marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease