Role Of Inflammation In Cancer Research Articles

Driving disruption in the solid tumor space: is it time to shift paradigms and develop novel immuno-oncology strategies?

Roisin McGuigan, Editor, Cell & Gene Therapy Insights, speaks to Edward Patz, Chief Executive Officer, Grid Therapeutics, LLC; James and Alice Chen Distinguished Professor of Radiology, Professor in Pharmacology and Cancer Biology, Duke University School of MedicineEdward Patz, Jr is a founder and the CEO of Grid Therapeutics. He is also the James and Alice Chen Distinguished Professor of Radiology and a Professor in Pharmacology and Cancer Biology at Duke University School of Medicine. He began his training in High Energy Physics at Harvard University, received his MD from the University of Maryland, completed his residency and thoracic imaging fellowship at the Brigham and Women’s Hospital and Harvard Medical School, and then was appointed to the faculty in the Department of Radiology at the Brigham, Harvard Medical School, and the Dana Farber Cancer Institute. In 1991, he was recruited to the Thoracic Imaging section in the Department of Radiology at Duke. Dr Patz is a clinician–scientist, with over 200 publications, and has participated in numerous clinical trials including the National Lung Cancer Screening Trial (NLST). For over 25 years, he has been the principal investigator of a basic science laboratory that explores clonal evolution of tumors, biomarkers for early detection, and the role of inflammation in cancer.

Nutrition in cancer therapy: Overview for the cancer patient.

Despite significant advances in oncologic treatment, cancer-associated metabolic derangements largely remain poorly understood and are often neglected in cancer care. Cancer cachexia and metabolic changes exhibited by neoplastic cells pose formidable barriers to improving outcomes and quality of life. Although cancer has traditionally been viewed as a proliferative disease caused by genetic mutations, newer perspectives suggest that it is primarily a metabolic disease. This paper discusses the etiology of cachexia and sarcopenia and nutrition interventions that can address these wasting disorders. The role of inflammation in cancer and the methods for preventing and resolving inflammation with nutrition intervention are also explored. Several nutrition recommendations aimed at overcoming cachexia, resolving inflammation, and improving cancer outcomes are provided based on current literature. This manuscript selected only a few areas on which to focus and is not all-inclusive of the expansive literature available on the topic of cachexia.

Historia badań nad rolą zapalenia w onkologii

Przebieg procesu zapalnego w ciele człowieka obserwowano i opisywano już w czasach starożytnych. Wraz z rozwojem współczesnej patologii i immunologii w XIX i XX wieku zaczęto obserwować powiązania między nowotworzeniem a reakcją zapalną. Choć pierwsze doniesienia łączące ze sobą te dwa procesy datuje się na pierwszą połowę XIX wieku, to dopiero dalsze badania pozwoliły na zrozumienie oddziaływania tych procesów. Najnowsze doniesienia coraz częściej pokazują, że reakcja zapalna odgrywa bardzo ważną rolę w progresji choroby nowotworowej. Proces nowotworzenia w wielu przypadkach, jak na przykład nowotwory przewodu pokarmowego, rozpoczyna się od przewlekłego zapalenia i infekcji. Obecnie wiemy także, że reakcja zapalna często występuje w mikrośrodowisku nowotworu stymulując proliferację i migrację komórek nowotworowych. Celem tej pracy jest przybliżenie historii badań nad reakcją zapalną w nowotworzeniu, od pierwszej obserwacji tej zależności do najnowszych doniesień.

Abstract 4625: Mouse strains for cancer research at The Jackson Laboratory Repository

Abstract Genetically defined mice have been the cornerstone of cancer research and resources at The Jackson Laboratory since the founding of the laboratory nearly nine decades ago. The Jackson Laboratory distributes more than 10,500 strains to the scientific community, many with applications in cancer research, including mouse models for specific cancers, xenograft models, immunodeficient platforms for PDX studies, multi-purpose “tool strains” (such as CRISPR cas9-expressing lines), recombinase expressing strains, as well as conditional and inducible expression lines (such as Cre-lox). New to the JAX Repository collection is a KrasLSL-A146T strain with inducible mutant Kras A146T for use in research of gastrointestinal tract and hematological cancers. The tamoxifen-inducible model for pancreatic ductal adenocarcinoma (PDAC), KPCX, and the related conditional activatable Kras allele/floxed Trp53 double mutant line, KP, have recently been developed. Inducible expression of mutant human speckle-type POZ protein (SPOP) in one newly acquired line allows study of prostate tumorigenesis. The portfolio of strains useful for engraftment studies has expanded, complementing the versatile humanized NOD scid gamma (NSG) platform lines. For custom generation of mutant strains, the Repository distributes a variety of research tool strains such as cas9-expressing lines, both constitutive expressing and Cre-inducible models, on different defined genetic backgrounds. Other recently added mutants allow research of the role of inflammation in cancer and screening immunomodulatory cancer therapies. In addition to safeguarding each strain by cryopreservation, the Repository‘s comprehensive quality control program confirms mutation identity and genetic background, and screens for unwanted alleles (such as stray GFP, cre, lacZ, etc.). Investigators can search for specific strains on the JAX Mice website, or peruse the Oncology Therapeutic Area webpage for cancer research related strains and resources. Researchers can submit their strains to be considered for inclusion in the Repository on The Jackson Laboratory website: www.jax.org/donate-a-mouse The Jackson Laboratory Repository is supported by the NIH, The Howard Hughes Medical Institute, and other private charitable foundations. Citation Format: Deborah Boswell, Stephen Rockwood, Cathleen Lutz, The JAX Repository Team. Mouse strains for cancer research at The Jackson Laboratory Repository [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4625.

Expression of inflammatory molecules cyclooxygenase-2 and forkhead box protein 3 in Wilms’ tumor microenvironment and their clinicopathological significance

Background and purpose The role of inflammation in cancer has been reported in various adult malignant neoplasms. Cyclooxygenase-2 (COX-2) is overexpressed in invasive breast carcinoma, colonic adenocarcinomas, as well as other tumors, and inhibitors of COX-2 have increasingly become therapeutic alternatives in many tumors. Forkhead box protein 3 (FOXP-3) transcription factor is important for the development of Tregs and hence maintenance of immunologic self-tolerance. Activity of Tregs is increased in lung cancer, gastric, and several adult-onset tumors, and they play a role in suppressing the antitumor immune responses. However, the exact role of these inflammatory molecules in pediatric malignancies especially Wilms’ tumor (WT) has not yet been fully addressed. Aim The aim of the present study was to investigate the expression of the inflammatory molecules COX-2 and FOXP-3 in WTs and their possible association with the different clinicopathological parameters. Patients and methods In this study, 21 formalin-fixed paraffin-embedded specimens of WTs were evaluated. Anaplasia [unfavorable histology (UFH)] was found in 31.6% of the studied tumors. Protein expression of COX-2 and FOXP-3 was investigated using immunohistochemistry. The degree of expression of both COX-2 and FOXP-3 expression was semiquantitatively assessed for each of the studied tumors using modified H-scoring. Results The present study revealed that COX-2 was expressed in the cytoplasm of all studied cases (100%). Its expression was higher in anaplastic WT (UFH) (median H-score, 200) compared with tumors with favorable histology (median H-score, 160). However, this difference was not statistically significant (P=0.167). On the contrary, FOXP-3 expression in WT was mostly low. Its expression varied between an H-score of 10 and 130 (median, 20). No significant difference in expression was noted between favorable histology versus UFH tumors. The present study also demonstrated a significant positive association between expression of COX-2 and FOX-P3 in WTs (P=0.033). Conclusion Our results show that COX-2 is strongly expressed in all WTs with a trend toward higher expression in UFH ones. Furthermore, the significant association between COX-2 expression and FOXP-3 expression in the studied cases suggests that inhibition of COX-2 may lead to an associated suppression of FOXP-3 activity and thereby enhancing the antitumor immune responses in these patient, which is an interesting finding that needs to be further explored.

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14.

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Inflammation and Notch signaling: a crosstalk with opposite effects on tumorigenesis

The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1–4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, DLL3 or DLL4) or non-canonically (through various molecules shared by other pathways). In the context of tumor biology, the deregulation of Notch signaling is found to be crucial, but it is still not clear if the activation of this pathway exerts a tumor-promoting or a tumor suppressing function in different cancer settings. Untill now, it is well known that the inflammatory compartment is critically involved in tumor progression; however, inflammation, which occurs as a physiological response to damage, can also drive protective processes toward carcinogenesis. Therefore, the role of inflammation in cancer is still controversial and needs to be further clarified. Interestingly, recent literature reports that some of the signaling molecules modulated by the cells of the immune system also belong to or interact with the canonical and non-canonical Notch pathways, delineating a possible link between Notch activation and inflammatory environment. In this review we analyze the hypothesis that specific inflammatory conditions can control the activation of the Notch pathway in terms of biological effect, partially explaining the dichotomy of both phenomena. For this purpose, we detail the molecular links reported in the literature connecting inflammation and Notch signaling in different types of tumor, with a particular focus on colorectal carcinogenesis, which represents a perfect example of context-dependent interaction between malignant transformation and immune response.

Using Immune Marker Panels to Evaluate the Role of Inflammation in Cancer: Summary of an NCI-sponsored Workshop.

Chronic inflammation is recognized to play a role in the development of several cancers. Past investigations of inflammation and cancer have typically been small, used varied assay platforms, and included a narrow range of analytes. Multiplex technologies have now been developed to measure larger numbers of inflammatory markers using small volumes of specimens. This has created an opportunity for systematic, large-scale epidemiological studies to evaluate the role of inflammation in cancer. However, lack of consensus on the approach to these studies, the technologies/assays to be used, and the most adequate analysis/interpretation of findings have thus far hindered progress. In June of 2014, the National Cancer Institute convened a workshop involving epidemiologists, immunologists, statisticians, and laboratory biologists to share their experiences with new inflammation marker technologies and findings from association studies using such methods and technologies (http://epi.grants.cancer.gov/workshops/). Consensus and gaps in our understanding of the role of chronic inflammation in cancer were identified and recommendations made to improve future efforts in this area. These recommendations are summarized herein, along with specific suggestions for how they may be implemented. By facilitating discussions among various groups, and encouraging interdisciplinary collaborations, we anticipate that the pace of research in this field will be accelerated and duplication of efforts can be minimized.

Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells

The role of inflammation in cancer is controversial as both tumor-promoting and tumor-suppressive aspects of inflammation have been reported. In particular, it has been shown that pro-inflammatory cytokines, like interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor α (TNFα), may either promote or suppress cancer. However, the cellular and molecular basis underlying these opposing outcomes remains enigmatic. Using mouse models for myeloma and lymphoma, we have recently reported that inflammation driven by tumor-specific T helper 1 (Th1) cells conferred protection against B-cell cancer and that interferon-γ (IFN-γ) was essential for this process. Here, we have investigated the contribution of several inflammatory mediators. Myeloma eradication by Th1 cells was not affected by inhibition of TNF-α, TNF-related weak inducer of apoptosis (TWEAK), or TNF-related apoptosis-inducing ligand (TRAIL). In contrast, cancer elimination by tumor-specific Th1 cells was severely impaired by the in vivo neutralization of both IL-1α and IL-1β (collectively named IL-1) with IL-1 receptor antagonist (IL-1Ra). The antitumor functions of tumor-specific Th1 cells and tumor-infiltrating macrophages were both affected by IL-1 neutralization. Secretion of the Th1-derived cytokines IL-2 and IFN-γ at the incipient tumor site was severely reduced by IL-1 blockade. Moreover, IL-1 was shown to synergize with IFN-γ for induction of tumoricidal activity in tumor-infiltrating macrophages. This synergy between IL-1 and IFN-γ may explain how inflammation, when driven by tumor-specific Th1 cells, represses rather than promotes cancer. Collectively, the data reveal a central role of inflammation, and more specifically of the canonical pro-inflammatory cytokine IL-1, in enhancing Th1-mediated immunity against cancer.

Mutant p53 Reprograms TNF Signaling in Cancer Cells through Interaction with the Tumor Suppressor DAB2IP

Inflammation is a significant factor in cancer development, and a molecular understanding of the parameters dictating the impact of inflammation on cancers could significantly improve treatment. The tumor suppressor p53 is frequently mutated in cancer, and p53 missense mutants (mutp53) can acquire oncogenic properties. We report that cancer cells with mutp53 respond to inflammatory cytokines increasing their invasive behavior. Notably, this action is coupled to expression of chemokines that can expose the tumor to host immunity, potentially affecting response to therapy. Mechanistically, mutp53 fuels NF-κB activation while it dampens activation of ASK1/JNK by TNFα, and this action depends on mutp53 binding and inhibiting the tumor suppressor DAB2IP in the cytoplasm. Interfering with such interaction reduced aggressiveness of cancer cells in xenografts. This interaction is an unexplored mechanism by which mutant p53 can influence tumor evolution, with implications for our understanding of the complex role of inflammation in cancer.

Characterization of the Inflammatory Microenvironment and Identification of Potential Therapeutic Targets in Wilms Tumors

The role of inflammation in cancer has been reported in various adult malignant neoplasms. By contrast, its role in pediatric tumors has not been as well studied. In this study, we have identified and characterized the infiltration of various inflammatory immune cells as well as inflammatory markers in Wilms tumor (WT), the most common renal malignancy in children. Formalin-fixed paraffin-embedded blocks from tumors and autologous normal kidneys were immunostained for inflammatory immune cells (T cells, B cells, macrophages, neutrophils, and mast cells) and inflammatory markers such as cyclooxygenase-2 (COX-2), hypoxia-inducible factor 1α, phosphorylated STAT3, phosphorylated extracellular signal–related kinases 1 and 2, inducible nitric oxide synthase, nitrotyrosine, and vascular endothelial growth factor expression. Overall, we found that there was predominant infiltration of tumor-associated macrophages in the tumor stroma where COX-2 was robustly expressed. The other tumor-associated inflammatory markers were also mostly localized to tumor stroma. Hence, we speculate that COX-2–mediated inflammatory microenvironment may be important in WT growth and potential therapies targeting this pathway may be beneficial and should be tested in clinical settings for the treatment of WTs in children.

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.

The role of inflammation in prostate cancer.

In the United States and in "Westernized" countries, the prevalence of both prostate cancer and prostate inflammation is very high, indicating that the two pathologies could be causally related. Indeed, chronic inflammation is now regarded as an "enabling" characteristic of human cancer. Prostate cancer incidence is thought to be mediated in part by genetics, but also by environmental exposures, including the same exposures that may contribute to the development of prostatic inflammation. As our understanding of the role of inflammation in cancer deepens, it is increasingly apparent that "inflammation" as a whole is a complex entity that does not always play a negative role in cancer etiology. In fact, inflammation can play potentially dichotomous (both pro and antitumorigenic) roles depending on the nature and the cellular makeup of the immune response. This chapter will focus on reviewing the current state of knowledge on the role of innate and adaptive immune cells within the prostate tumor microenvironment and their seemingly complex role in prostate cancer in preventing versus promoting initiation and progression of the disease.

Cancer risk in immune-mediated inflammatory diseases (IMID)

Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response against the tumor and immunosuppression is known to increase the risk for certain tumors.This article reviews current literature on the role of inflammation in cancer and the cancer risk in immune-mediated inflammatory diseases (IMIDs). We discuss the effect on cancer risk of different drug classes used in the treatment of IMIDs treatment, including biologicals such as tumor necrosis factor (TNF) inhibitors.Overall cancer incidence and mortality risk are similar to the general population in inflammatory bowel disease (IBD), and slightly increased for rheumatoid arthritis and psoriasis, with risk profiles differing for different tumor types. Increased risk for non-melanoma skin cancer is associated with thiopurine treatment in IBD, with the combination of anti-TNF and methotrexate in rheumatoid arthritis and with PUVA, cyclosporine and anti-TNF treatment in psoriasis. Data on the safety of using biologic or immunosuppressant therapy in IMID patients with a history of cancer are scarce.This review provides clinicians with a solid background to help them in making decisions about treatment of immune-mediated diseases in patients with a tumor history.This article is related to another review article in Molecular Cancer: http://www.molecular-cancer.com/content/12/1/86.

Preliminary Insights on the Role of Inflammation in Cancer

Preliminary Insights on the Role of Inflammation in Cancer

CCAAT/Enhancer-binding Protein δ Mediates Tumor Necrosis Factor α-induced Aurora Kinase C Transcription and Promotes Genomic Instability

Epidemiologic and clinical research indicates that chronic inflammation increases the risk of certain cancers, possibly through chromosomal instability. However, the mechanism of inflammation-dependent chromosomal instability associated with tumorigenesis is not well characterized. The transcription factor CCAAT/enhancer-binding protein δ (C/EBPδ, CEBPD) is induced by tumor necrosis factor α (TNFα) and expressed in chronically inflamed tissue. In this study, we show that TNFα promotes aneuploidy. Loss of CEBPD attenuated TNFα-induced aneuploidy, and CEBPD caused centromere abnormality. Additionally, TNFα-induced CEBPD expression augmented anchorage-independent growth. We found that TNFα induced expression of aurora kinase C (AURKC) through CEBPD, and that AURKC also causes aneuploidy. Furthermore, high CEBPD expression correlated with AURKC expression in inflamed cervical tissue specimens. These data provide insight into a novel function for CEBPD in inducing genomic instability through the activation of AURKC expression in response to inflammatory signals.

Inflammation and cancer: tumor initiation, progression and metastasis, and Chinese botanical medicines

Both historically and contemporarily, cancer is seen as an inflammatory process. Evidence has emerged in the last two decades that at the molecular level most chronic diseases, including cancer, are caused by a dysregulated inflammatory response. The identification of transcription factors such as nuclear factor-kappa B and signal transducer and activator of transcription 3 and their gene products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines, cyclooxygenase-2, and vascular endothelial growth factor, adhesion molecules and others has provided the molecular basis for the role of inflammation in cancer. Tumor initiation, its progression and metastasis and the failure of immune suppression of tumors all can be attributed in part to chronic and systemic inflammation. Chinese herbs have a long history in both treatment of cancer and suppression of inflammation. This paper looks at recent research on cancer and inflammation and Chinese herbs and compounds, which can be used in the treatment of cancer.

The resolution of inflammation and cancer

Inflammation has long been thought to contribute to the development of cancer; however there is also clear evidence that the immune system can recognize and eliminate cancer cells. Current research suggests that cancer-associated inflammation has a dual role in tumor progression; inflammatory mediators promote the malignant activity of cancer cells by acting as growth factors and also stimulate angiogenesis, however, cancer-associated inflammation is also linked with immune-suppression that allows cancer cells to evade detection by the immune system. In this review we will discuss the dual role of inflammation in cancer and how endogenous anti-inflammatory mechanisms may equally be important in carcinogenesis.

Inflammation and cancer: how friendly is the relationship for cancer patients?

Evidence has emerged in the last two decades that at the molecular level most chronic diseases, including cancer, are caused by a dysregulated inflammatory response. The identification of transcription factors such as NF-kappaB, AP-1 and STAT3 and their gene products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines, cyclooxygenase-2, 5 lipooxygenase, matrix metalloproteases, and vascular endothelial growth factor, adhesion molecules and others have provided the molecular basis for the role of inflammation in cancer. These inflammatory pathways are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, which together account for as much as 95% of all cancers. These pathways have been implicated in transformation, survival, proliferation, invasion, angiogenesis, metastasis, chemoresistance, and radioresistance of cancer, so much so that survival and proliferation of most types of cancer stem cells themselves appear to be dependent on the activation of these inflammatory pathways. Most of this evidence, however, is from preclinical studies. Whether these pathways have any role in prevention, progression, diagnosis, prognosis, recurrence or treatment of cancer in patients, is the topic of discussion of this review. We present evidence that inhibitors of inflammatory biomarkers may have a role in both prevention and treatment of cancer.

Role of adipose hypoxia in endocrine alterations: a possible new anti-inflammatory therapeutic target in obesity?

Dr Jianping Ye is a Professor at the Pennington Biomedical Research Center, Louisiana State University (LA, USA). He completed his graduate education in the medical school, Beijing University (China) in 1989 and moved to the USA to undertake postdoctoral research in 1992. He conducted research in the role of inflammation in cancer and was an instructor at the Health Science Center at San Antonio, University of Texas (TX, USA) in 1997, and assistant professor in the West Virginia University (WV, USA) in 1999. In 2001, he set up his lab at the Pennington Biomedical Research Center, Louisiana State University, where obesity research is the main focus. His current work, supported by NIH and American Diabetes Association, predominantly focuses on insulin resistance in obesity. Recent work from his lab reported that adipose hypoxia may contribute to chronic inflammation and insulin resistance in obesity. The study was based on the hypoxia effect on the endocrine function of adipocytes in a preliminary study of large adipocytes in his laboratory in 2004. Here, Nicole Nogoy talks to Jianping Ye on the future and current issues in the cellular and molecular mechanisms of insulin resistance.