Contributions to microbiology最新文献

Detection and observation of primary tumor growth and metastasis in living subjects is an important task in clinical and basic cancer research. Recently several approaches and techniques emerged which offer a huge variety of options with respect to the specific objectives and questions of a given study. Recent developments in the field of in vivo imaging not only allow the assessment of anatomic information but also functional processes with cellular resolution and molecular sensitivity. This chapter will provide an overview of the most common imaging techniques which are currently available for the detection and observation of metastasizing tumor cells. General capacities, advantages, limitations and drawbacks will be discussed. These techniques include computed tomography (CT), molecular resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), fluorescence imaging (FI), and bioluminescent imaging (BLI). The objective is to provide the cancer researcher with information that will help solve the dilemma of how best to apply the latest imaging tools for studying biological questions in the context of the living body.

The overall mechanism of bone marrow-derived stem cell (BMDC) trans-differentiation seems to be simple: BMDCs trans-differentiate as referred to the blueprint, which is given by the tissue itself. Thereby, the blueprint can be the local tissue micro-environment (defined by the tissue-specific cytokine, chemokine, adhesion molecule pattern, etc.), it can be a single cell (cell fusion), or it can be a combination of both. In fact stem cell trans-differentiation is a complex not yet fully understood process. In between the start- and stop-points of transdifferentiation several gene reprogramming steps have to occur in a sequential step-by-step manner, for which a defined set of instructions is a prerequisite to ensure an accurate transdifferentiation. However, a recent study indicated that the ability of BMDCs - to adopt tissue function by reading its blueprint - seems to be a double-edged sword since BMDCs that have received a faulty blueprint, provided by chronically inflamed tissue, trans-differentiated into a neoplastic phenoytpe. Here, we review the importance of an accurate blueprint for BMDC trans-differentiation and discuss a model showing that BMDCs might contribute to overall tumor development due to recruitment to tumor tissue.

Oncogenic viruses are important pathogens in farm and companion animals. These original pathogens are classified in various virus families, such as Retroviridae, Papillomaviridae, and Herpesviridae. Besides a role as pathogens for its original host, animal viruses serve as valuable models for viruses affecting humans, such as hepatitis B virus, and issues of immunity, therapy, but also basic pathophysiological mechanisms, can often only be addressed in those animal systems.

Conventional genetic theories have failed to explain why cancer (1) is not found in newborns and thus not heritable; (2) develops only years to decades after 'initiation' by carcinogens; (3) is caused by non-mutagenic carcinogens; (4) is chromosomally and phenotypically 'unstable'; (5) carries cancer-specific aneuploidies; (6) evolves polygenic phenotypes; (7) nonselective phenotypes such as multidrug resistance, metastasis or affinity for non-native sites and 'immortality' that is not necessary for tumorigenesis; (8) contains no carcinogenic mutations. We propose instead that cancer is a chromosomal disease: Accordingly, carcinogens initiate chromosomal evolutions via unspecific aneuploidies. By unbalancing thousands of genes aneuploidy corrupts teams of proteins that segregate, synthesize and repair chromosomes. Aneuploidy is thus a steady source of karyotypic-phenotypic variations from which, in classical Darwinian terms, selection of cancer-specific aneuploidies encourages the evolution and subsequent malignant 'progressions' of cancer cells. The rates of these variations are proportional to the degrees of aneuploidy, and can exceed conventional mutation by 4-7 orders of magnitude. This makes cancer cells new cell 'species' with distinct, but unstable karyotypes, rather than mutant cells. The cancer-specific aneuploidies generate complex, malignant phenotypes, through the abnormal dosages of the thousands of genes, just as trisomy 21 generates Down syndrome. Thus cancer is a chromosomal rather than a genetic disease. The chromosomal theory explains (1) nonheritability of cancer, because aneuploidy is not heritable; (2) long 'neoplastic latencies' by the low probability of evolving competitive new species; (3) nonselective phenotypes via genes hitchhiking on selective chromosomes, and (4) 'immortality', because chromosomal variations neutralize negative mutations and adapt to inhibitory conditions much faster than conventional mutation. Based on this article a similar one, entitled 'The chromosomal basis of cancer', has since been published by us in Cellular Oncology 2005;27:293-318.

During the past two to three decades there has been an exciting revolution in our understanding of the multistage carcinogenic process and of the molecular genetics of cancer. The general principle of multifactor interactions is central to our understanding of cancer causation. The paradigm that persistent infections and chronic inflammation contributes via cytokine- and chemokine-mediated disbalanced immune response to carcinogenesis becomes more and more attractive in cancer research. Besides genetic factors, the epigenetics of impaired cell signaling and signal transduction by proinflammatory cytokines and chemokines are important potentiators of carcinogenesis. The activation of the nuclear factor kappaB, for example, a hallmark of inflammatory responses that is frequently detected in tumors, might constitute a missing link between inflammation and cancer. It will be a challenge for future therapeutic and preventive cancer research to detect potential targets in chronic inflammatory disease which are essential links to promote inflammation-associated cancer.

Rudolf Ludwig Carl Virchow (1821-1902) studied medicine and received his academic degree 'Dr. med.' in 1843. In 1856 he was appointed as head of the institute of pathology at the University of Berlin. In 1859, he became a member of the Berlin town council and later additionally a member of the Prussian and the German parliament. With his probably most important publication 'Cellularpathologie' he introduced pathology to a cellular rationale. This was the major basis for his research in oncology. Virchow further studied aspects of inflammation, despite only few links to tumor pathology were drawn. The few links from infection and inflammation to tumor pathology have almost been forgotten or ignored and have never been evaluated and discussed sufficiently. Virchow recognized that inflammation is a pre-disposing factor for tumor genesis. Furthermore, infectious diseases such as syphilis and tuberculosis had elements of a 'tumor process' and were therefore often difficult or impossible to separate from a 'genuine' tumor process, which was recognized by him. He further tried to explain tumor dissemination by an 'infectious' process. Additionally, there were ideas for a coherent explanation of tumor etiology in form of a common bacterial pathogen ('Krebsbacillus').

Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.