Common Tumor Entity Research Articles

Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer

Regulatory (FOXP3+) T cells (Tregs) comprise a subpopulation of CD4+ T cells that suppress autoreactive immune cells, thereby protecting organs and tissues from autoimmunity. Tregs have also been detected in human malignancies and their depletion or inactivation substantially improves cellular antitumor immunity in preclinical studies. Novel therapeutic strategies for cervical cancer and precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination approaches. In this context, the frequency of Tregs in cervical cancer and precancerous CIN could influence therapeutic strategies. We determined the frequency of infiltrating CD4+ and CD8+ T cells as well as FOXP3+ Tregs in high-grade CIN lesions (CIN III) and cervical carcinoma compared to colon carcinoma, skin melanoma, and bronchial carcinoma. We show that human papilloma virus-derived lesions have a significantly higher number of infiltrating lymphocytes and FOXP3+ Tregs compared to three other common tumor entities. In addition we explored the therapeutic effect of agonistic anti-glucocorticoid-induced tumor necrosis factor receptor family-related protein antibodies that, by single systemic application, inactivate Tregs and induce strong intratumoral invasion of CD8+ T cells and complete tumor eradication in 70% of treated animals. The large number of Tregs in human papilloma virus-derived lesions suggests a pivotal role of Tregs for counteracting the host immune response. We therefore regard CIN and cervical cancer as prime targets for new immune-based non-invasive therapies.

Proteomic analysis of protein expression in human tonsillar cancer differentially expressed proteins characterize human tonsillar cancer

Background. Head and neck cancer continues to be one of the most common tumor entities worldwide. Within this group of malignancies, tonsillar squamous cell carcinoma represent approximately 15–20% of all intraoral and oropharyngeal carcinomas in the United States. Accurate and early stage diagnosis still remains a major challenge, as patients are often presented at an advanced stage of disease, causing a low overall survival rate. Thus, new diagnostic markers are highly desirable and could allow for a more reliable diagnosis, with further insights into carcinogenesis and tumor biology. Furthermore, these markers could be the basis for new therapeutic targets and early disease detection. To address these issues, we decided to use a global proteomic approach to characterize tonsillar squamous cell carcinoma. Materials and methods. A total of 19 tonsillar carcinoma samples and 12 benign controls acquired from the corresponding normal epithelium were analyzed by 2-D gel electrophoresis. 2-DE gels were silver stained and analyzed using the PDQuest analysis software (BioRad). Tumor specific spots were detected and identified by consecutive MALDI-TOF-MS or MS/MS polypeptide identification. Results. In total, 70 proteins showed significant quantitative differences in protein expression, with 50 polypeptides accessible for identification. Of those 50 polypeptides, we were able to identify a total of 27 proteins and protein isoforms, significantly up- or down-regulated in tonsillar cancer samples. In addition to previously reported polypeptides in head and neck cancers, we were able to identify several new potential marker proteins in this study. Conclusion. Our results show that a combination of tonsillar cancer specific proteins can be used for histopathological diagnosis and may serve as a basis for discovering further biomarkers for early detection and prediction of response to treatment in the future.

Brain Tumors in Children: Initial Symptoms and Their Influence on the Time Span Between Symptom Onset and Diagnosis

Brain tumors are the most common solid tumor entity in childhood. Symptoms are often unspecific, depending not only on the localization of the tumor, but also on the age of the child. The aim of this study was to detect factors influencing the time span between the occurrence of symptoms and the diagnosis to alert health professionals to the early symptoms of pediatric brain tumors. The records of 245 consecutive patients treated for brain tumors between 1980 and 2004 at the neuropediatric department of the University of Muenster were analyzed regarding their primary symptoms, tumor location, entity, and, in 151 cases, the primary electroencephalogram findings. The median time span between symptom onset and diagnosis in our study was 24 days. Multivariate analysis showed a significant influence of 6 parameters on the interval between symptom onset and diagnosis. An additional symptom had a significant influence on the time span between symptom onset and diagnosis in the univariate analysis. The findings that several symptoms influence the interval between symptom onset and diagnosis emphasize the necessity to systematically inquire about the key symptoms of brain tumors. The challenge for every consultant is to decide in which cases cerebral imaging is appropriate. As the most frequent symptoms are unspecific and often underestimated, a detailed anamnesis is crucial to detect possible brain tumor patients. In doubtful cases, a systematic interrogation regarding the catalogue of symptoms can be helpful.

Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence.

Brain tumors amount to less than 2% of all malignant neoplasms. However, they account for approximately 20% of all childhood cancers and are the leading cause of cancer mortality among children. Recently, enormous progress has been achieved in the field of pediatric neuro-oncology regarding the classification of children's brain tumors, as well as the understanding of the genetic events involved in their pathogenesis; thus leading to an emerging role of molecular diagnostic approaches using novel tools. Comparative genomic hybridization (CGH) is a technique that has revolutionized cytogenetic knowledge in the past decade. It permits the detection of chromosomal copy number changes without the need for cell culturing and gives a global overview of chromosomal gains and losses throughout the whole genome of a tumor. A survey of CGH-related publications on central and peripheral nervous system tumors in the pediatric and adolescent population revealed 884 cases. The CNS tumor groups most frequently examined by CGH were embryonal tumors (268 cases/30.3%) and ependymomas (241/27.2%), followed by astrocytic (163/18.4%), peripheral nerve (73/8.2%), choroid plexus tumors (56/6.3%), and craniopharyngiomas (38/4.3%). The most common CNS tumor entities were medulloblastomas (238/26.9%), classic ependymomas (160/18.1%), anaplastic ependymomas (70/7.9%), pleomorphic xanthoastrocytomas (53/6.0%), and pilocytic astrocytomas (50/5.6%). This article provides a short review of the CGH technique and its pitfalls, summarizes the current CGH-related data on pediatric brain tumors and muses on the future of CGH.

Diagnostic imaging in clinical tumor staging

In order to evaluate the anatomic extension of neoplastic disease according to the TNM system sufficiently, inclusion of imaging techniques is absolutely necessary. In addition, decisions on further clinical processing are based on precise identification of primary tumor extent (T), condition of regional nodes (N) and possible presence of distant metastases (M). Breast cancer, lung cancer, colorectal cancer and prostate cancer represent the most common tumor entities. Within this context the importance of imaging techniques for diagnosis, prognosis, therapy and follow-up of patients with these malignancies is presented in this report.