Special Issue "Exploring Inflammation in Cancers"

Guest Editor
Prof. Dr. Masanobu Oshima
Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
E-Mail: oshimam@staff.kanazawa-u.ac.jp
Phone: +81-76-264-6760
Fax: +81-76-234-4519
Interests: cancer genetics; molecular pathology of gastrointestinal cancers; cancer stem cell and Wnt signaling

Dear Colleagues,

Epidemiological studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of cancer development. NSAIDs exert their anti-inflammatory activity through the inhibition of cyclooxygenase-2 (COX-2), resulting in suppression of prostaglandin E₂ (PGE₂) biosynthesis. Consistently, genetic studies using mouse models have demonstrated that a proinflammatory prostaglandin PGE₂ plays an essential role in gastrointestinal cancer development through induction of angiogenesis or suppression of tumor immunity. On the other hand, NF-kB and Stat3 are two major transcription factors in the inflammatory response, which are activated by TNF-a and IL-6, respectively. It has been shown that activation of both NF-kB and Stat3 is required for colitis-associated cancer development in mouse models through inhibition of apoptosis and acceleration of cell proliferation. These results, taken together, indicate that inflammatory signaling networks promote tumor development through multiple pathways. Moreover, recent studies have also indicated that inflammation causes tumor initiation by induction of epigenetic or genetic alterations, and malignant progression through remodeling the metastatic microenvironment. Accordingly, it is possible that targeting inflammation is an effective therapeutic strategy against cancer initiation, promotion and progression. This special issue on “Exploring Inflammation in Cancers” will include original research articles and review papers in the field of inflammation and cancer, including, but not limited to, infection-associated cancer (H. pylori, HCV etc.), cytokine/chemokine signaling in cancer development, innate immunity and acquired immunity (Th1, Th2 or Th17) in cancer development, tumor-associated macrophages (TAMs) in tumorigenesis, and inflammation and epigenetics. Thank you for your collaboration.

Prof. Dr. Masanobu Oshima
Guest Editor

Submission

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• inflammation
• COX-2
• PGE2
• TNF-alpha
• NF-kappa B
• Stat3
• tumor-associated macrophages
• colitis-associated cancer
• innate immunity

Type of Paper: Article
Title: Tumour-Associated Macrophages Produce Original Matrix-Related Molecules that Sustain the Reactive Stroma of Cancer
Author: Paola Allavena
Affiliation: Dpartment of Immunology and Inflammation, Istituto Clinico Humanitas, Milano, Italy; E-Mail: Paola.Allavena@humanitasresearch.it
Abstract: Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors and actively participate in the deposition and degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of growth factors and promotes tumor cell invasion. The RNA profiling of human TAM and of in vitro tumor-conditioned macrophages revealed the expression of a matrix-related signature, with the up-regulation of genes coding for different matrix proteins and for several extra-cellular and intra-cellular proteolytic enzymes. The focus of this paper will be on two poorly characterized matrix proteins produced by tumor macrophages: an unusual fibronectin isoform and Osteoactivin. In addition to serve as structural proteins, these two components appear to play key functions in the regulation of the vessel network, induction of tumor cell motility and degradation of cellular debris. These functions co-operate to the maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

Type of Paper: Article
Title: Leukotriene Receptors Are Overexpressed in Gastric Cancer
Authors: M. Venerito, D. Kuester, C. Harms, D. Schubert, P. Malfertheiner and T.Wex
Affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Department of Pathology, Otto-von-Guericke University Hospital, Magdeburg, Germany
Abstract: Previously, we identified significant changes in the expression pattern of leukotriene receptors depending on the presence of Helicobacter pylori-mediated gastric inflammation. While the pathophysiological role of the eicosanoid pathway is well established for inflammatory process, its involvement in gastric cancer has not been studied. Methods: The expression of 5-Lipoxygenase (5-LOX) and receptors for leukotriene-B4 (BLT-1, BLT-2) and cysteinyl-leukotrienes (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in gastric cancer samples and in tumor-free mucosa from antrum and corpus of 35 consecutive patients who underwent gastrectomy. Results: Twenty-eight patients had gastric cancer of intestinal, 6 of diffuse and 1 of undifferentiated type. 5-LOX and both receptors (BLT-1, CysLT-1) were found to be expressed in 32/35, and 34/35 gastric cancer specimens, respectively. An increase in the immunohistochemical score of both receptors, but not of 5-LOX, was observed in gastric cancer compared to tumor-free gastric mucosa (BLT-1: 6.4±3.2 vs. 3±1.8, p<0.001; CysLT-1: 9.1±2.6 vs. 7.1±2.4 p<0.01; Mann-Whitney U-test). Data of BLT-2 and CysLT-2 are currently analyzed, and will be included in the manuscript. Conclusions: Leukotriene-receptors, but not 5-LOX, were expressed in tumor cell-lines and found to be up-regulated in gastric cancer tissue. The potential role of these receptors as prognostic and therapeutic target is discussed in context to the current literature.

Type of Paper: Review
Title: Unresolved Inflammation, Aging and Cancer: Framework for Design of Clinical Trials and Drug Development
Author: Mahin Khatami
Affiliation: National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA; E-Mail: Mkgoodness@aol.com
Abstract: Despite heavy public investment for over four decades on cancer war, progress in understanding the complex biology of cancer is still fragmentary.  Consequently, few projects have been successful in translating research into effective diagnosis, prevention and therapy while incidence of cancer is projected to rise in the next decade around the globe, particularly for the growing older population.  Numerous costly clinical trials and drug development projects and technologies are based on shut-gun findings of molecular entities from hundreds and thousands of molecules (e.g., altered gene, proteins/receptors, enzymes, lipids, cytokines/chemokines, metabolites, or regulatory cell components), claiming as targets for therapy, diagnosis or prevention of cancer without any tangible benefit for cancer-stricken public.   Moreover, few studies attempted to integrate the enormous amount of data that exist on multidisciplinary fields of cancer biology, to make sense of the relationships between data and pathways that are involved in carcinogenesis, or to connect the dots and to identify important knowledge gaps and missing links in order to form a clear vision of a big picture that would facilitate informed decision making on design of effective clinical trials or drug development.  The present article attempts to use relevant data on fundamental and primary roles that inflammation play in altering the dynamics of immune cell responses that further impact biology of aging body and increasing the risks of many chronic diseases and/or cancer. It is suggested that inflammation-induced alterations in cellular functions diversely manifest in immune-responsive and immune-privileged tissues leading to a wide range of age-associated illnesses.  Unresolved (persistent or recurrent) inflammation was recently defined as the loss of balance between two biologically opposing arms of acute inflammation termed ‘Yin’ (‘tumoricidal’) and ‘Yang’ (‘tumorigenic’) or apoptosis and wound healing properties of immune system.  Promotion of innate and adaptive immune cell function is likely the key in tumor surveillance ability of host tissue.  Identifying inflammation-induced time course kinetics of developmental phases of immune dysfunction are important first steps toward better understanding the biology cancer.  Framework for design of clinical trials and therapeutic approaches will be discussed based on a concept that inflammation is a common denominator in the genesis and progression of many chronic illnesses or cancer.