Konradin Metze

Gislaine B. Oliveira

Fernanda G. Pereira

Randall L. Adam

Irene Lorand-Metze

Spontaneous Apoptosis in Chronic Lymphocytic Leukemia Is Not an Independent Prognostic Factor for Stability of Disease When Compared with Combined AgNOR and TTM Scores

Invasive head and neck squamous carcinomas are among the cytogenetically most complex tumors. Perhaps for this reason, there is little consensus on the prognostic value of specific chromosomal aberrations. Here we present Results of CGH analysis of 56 clinically well-characterized set of head and neck cancers, consisting of larynx and pharynx only. The aim was to find possible associations with clinical outcome. The major chromosome arms showing gains were (in decreasing order): 3q, 7q, 8q, 5p, 11q13, 17q and 18p, and losses occurred at 3p, 11qter, 4p, 18q, and 5q. The segments most frequently amplified were 3q26-qter, 11q13, 11q22, 3q12&#x2013;13, 18p11.3, 18q11.2 and 8q24.3. Tumors with stages III and IV, and lymph node positive tumors had a worse clinical outcome. Surprisingly, no specific chromosomal abnormality correlated with disease-free survival. The only aberration that correlated to one of the clinico-pathological parameters was amplification 11q13, that occurred solely in lymph node positive, stage IV tumors. However 11q13 amplification did not correlate with disease-free survival. These Results seem to indicate that genetic alterations at the level of chromosomes have limited prognostic value in patients with invasive larynx and pharynx squamous cell carcinomas.

Mario Hermsen

Marta Alonso Guerv&#xf3;s

Gerrit Meijer

Paul van Diest

Carlos Su&#xe1;rez Nieto

Cesar Alvarez Marcos

Andr&#xe9;s Sampedro

Chromosomal Changes in relation to Clinical Outcome in Larynx and Pharynx Squamous Cell Carcinoma

Aims: To microscopically analyze the chemotherapeutic response of tumors using in vivo staining based on an annexinV-Cy5.5 probe and independently asses their apoptotic count using quantitative histological analysis. Methods: Lewis Lung Carcinomas cells, that are sensitive (CS-LLC) and resistant (CR-LLC) to chemotherapy were implanted in nude mice and grown to tumours. Mice were treated with cyclophosphamide and injected with a Cy5.5-annexinV fluorescent probe. In vivo imaging was performed using Fluorescence Molecular Tomography. Subsequently tumours were excised and prepared for histology. The histological tumour sections were stained for apoptosis using a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. A minimum of ten tissue sections were analyzed per tumour for apoptosis quantification by TUNEL staining and corresponding Cy5.5 distribution. Results: We detected higher levels of apoptosis and corresponding higher levels of Cy5.5 fluorescence in the CS-LLC vs. the CR-LLC tumours. The cell count rate on CS-LLC sections over CR-LLC was found to be &#x223c;2&#x2009;:1 where the corresponding area observed on Cy5.5 distribution measurements revealed a &#x223c;1.7&#x2009;:1 ratio of CS-LLC over CR-LLC. These observations are consistent with the higher apoptotic index expected from the CS-LLC cell line. Conclusions: Quantitative analysis of histological slices revealed higher fluorescence and higher apoptotic count in the CS-LLC tumour images compared to the CR-LLC tumour images. These observations demonstrate that the annexinV-Cy5.5 probe sensed the chemotherapeutic effect of cyclophospamide and further confirmed in vivo FMT measurements.

Heung Kook Choi

Doreen Yessayan

Hyun Ju Choi

Eyk Schellenberger

Alex Bogdanov

Lee Josephson

Ralph Weissleder

Vasilis Ntziachristos

Quantitative Analysis of Chemotherapeutic Effects in Tumors Using In Vivo Staining and Correlative Histology

Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFN&#x3B1; but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2&#x25;) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25&#x25; CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFN&#x3b3; producing CTL was reduced by 75&#x25; compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.

Hetty J. Bontkes

Janneke J. Ruizendaal

Marco W. J. Schreurs

Duco Kramer

Chris J. L. M. Meijer

Erik Hooijberg

Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors

Gene mutations play a critical role in cancer development and progression, and their identification offers possibilities for accurate diagnostics and therapeutic targeting. Finding genes undergoing mutations is challenging and slow, even in the post-genomic era. A new approach was recently developed by Noensie and Dietz to prioritize and focus the search, making use of nonsense-mediated mRNA decay (NMD) inhibition and microarray analysis (NMD microarrays) in the identification of transcripts containing nonsense mutations. We combined NMD microarrays with array-based CGH (comparative genomic hybridization) in order to identify inactivation of tumor suppressor genes in cancer. Such a &#x201c;mutatomics&#x201d; screening of prostate cancer cell lines led to the identification of inactivating mutations in the EPHB2 gene. Up to 8&#x25; of metastatic uncultured prostate cancers also showed mutations of this gene whose loss of function may confer loss of tissue architecture. NMD microarray analysis could turn out to be a powerful research method to identify novel mutated genes in cancer cell lines, providing targets that could then be further investigated for their clinical relevance and therapeutic potential.

Maija Wolf

Henrik Edgren

Aslaug Muggerud

Sami Kilpinen

Pia Huusko

Therese S&#xf8;rlie

Spyro Mousses

Olli Kallioniemi

NMD Microarray Analysis for Rapid Genome-Wide Screen of Mutated Genes in Cancer

G. A. Meijer

J. J. Oudejans

Targeted Therapies; Who Detects the Target&#x3F;

Mario Baumgart

Ernst Heinm&#xf6;ller

Olaf Horstmann

Heinz Becker

B. Michael Ghadimi

The Genetic Basis of Sporadic Pancreatic Cancer

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Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

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Chief Editor&nbsp;Professor Dimitrios Karamichos&nbsp;focuses on investigating corneal wound healing and dystrophies with a particular interest in the effect of transforming growth factor-β3 or TGF- β3 on corneal stromal cells and their extracellular environment.

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Analytical Cellular Pathology - Table of contents 2005

title

Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

Analytical Cellular Pathology