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Special Issue "Inflammation and Cancer"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2017)

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Guest Editor
Prof. Dr. Takuji Tanaka

Director, Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, Gifu, Japan
Website | E-Mail
Interests: colorectal carcinogenesis; inflammatory bowel disease; ulcerative colitis; Crohn’s disease; cancer chemiprevention; animal model
Guest Editor
Prof. Dr. Masahito Shimizu

Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1–1 Yanagido, Gifu 501–1194, Japan
Website | E-Mail
Interests: hepatocellular carcinoma; colorectal cancer; cancer chemoprevention; nutrition; retinoid; inflammation; obesity

Special Issue Information

Dear Colleagues,

Based on the data that are now available in the GLOBOCAN series of the IARC, there were 14.1 million new cases of cancer and 8.2 million cancer deaths in 2012. Among epithelial malignancies, some cancers have strong links to chronic inflammation and develop in the background of uncontrolled chronic inflammation. Although the mechanisms have not fully been elucidated, reactive oxygen and nitrogen species produced by inflammatory cells may cause DNA damage and mutations. These inflammatory cells are also able to produce and secrete a variety of cytokines and chemokines, some of which are known to affect tumor growth, metastasis, and angiogenesis.

The association between chronic inflammation and cancer is not a new concept. In 1863, Dr. Rudolf Virchow noticed, and first wrote about, the presence of leukocytes in neoplastic tissues. He later hypothesized that carcinogenesis could occur at sites of chronic inflammation and that uncontrolled chronic inflammation provides a favorable environment for cancer to form and grow. Today, oncologic data strongly support Virchow's intuition, confirming that some malignancies do not arise from infection and uncontrolled chronic inflammation. The last two decades of the 20th century were marked by the breathtaking evolution of molecular techniques in biology that consolidated the theoretical foundation of inflammation-associated carcinogenesis. Intriguingly, for both infection experts and oncologists, systemic inflammation appears to influence different phases of oncogenesis through different mechanisms.

In this light, this Special Issue entitled, “Inflammation and Cancer”, is well-timed to say the least, and provides a practical appreciation for the many biochemical, molecular, immunological, and cellular mechanisms shared by cancer and inflammatory processes.

Takuji Tanaka
Masahito Shimizu
Guest Editors

Manuscript Submission Information

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Keywords

  • inflammation
  • cancer
  • cytokines
  • gut microbiota
  • insulin resistance
  • molecular biology
  • obesity
  • adipose tissue
  • clinical trials

Related Special Issue

Published Papers (15 papers)

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Research

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Open AccessArticle Immunological and Inflammatory Impact of Non-Intubated Lung Metastasectomy
Int. J. Mol. Sci. 2017, 18(7), 1466; https://doi.org/10.3390/ijms18071466
Received: 4 April 2017 / Revised: 20 June 2017 / Accepted: 28 June 2017 / Published: 7 July 2017
Cited by 2 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text
Abstract
Background: We hypothesized that video-assisted thoracic surgery (VATS) lung metastasectomy under non-intubated anesthesia may have a lesser immunological and inflammatory impact than the same procedure under general anesthesia. Methods: Between December 2005 and October 2015, 55 patients with pulmonary oligometastases (at the first
[...] Read more.
Background: We hypothesized that video-assisted thoracic surgery (VATS) lung metastasectomy under non-intubated anesthesia may have a lesser immunological and inflammatory impact than the same procedure under general anesthesia. Methods: Between December 2005 and October 2015, 55 patients with pulmonary oligometastases (at the first episode) successfully underwent VATS metastasectomy under non-intubated anesthesia. Lymphocytes subpopulation and interleukins 6 and 10 were measured at different intervals and matched with a control group composed of 13 patients with similar clinical features who refused non-intubated surgery. Results: The non-intubated group demonstrated a lesser reduction of natural killer lymphocytes at 7 days from the procedure (p = 0.04) compared to control. Furthermore, the group revealed a lesser spillage of interleukin 6 after 1 (p = 0.03), 7 (p = 0.04), and 14 (p = 0.05) days. There was no mortality in any groups. Major morbidity rate was significantly higher in the general anesthesia group 3 (5%) vs. 3 (23%) (p = 0.04). The median hospital stay was 3.0 vs. 3.7 (p = 0.033) days, the estimated costs with the non-intubated procedure was significantly lower, even excluding the hospital stay. Conclusions: VATS lung metastasectomy in non-intubated anesthesia had significantly lesser impact on both immunological and inflammatory response compared to traditional procedure in intubated general anesthesia. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessArticle Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient Min Mice
Int. J. Mol. Sci. 2017, 18(5), 1058; https://doi.org/10.3390/ijms18051058
Received: 29 March 2017 / Revised: 5 May 2017 / Accepted: 9 May 2017 / Published: 14 May 2017
Cited by 1 | PDF Full-text (3036 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and is suggested to enhance cancer progression. In this study, the effect of deficiency of OPN on intestinal tumor development in
[...] Read more.
Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and is suggested to enhance cancer progression. In this study, the effect of deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was investigated. At 16 weeks of age, the number of small intestinal polyps in Min/OPN(+/−) and Min/OPN(−/−) mice was lower than that of Min/OPN(+/+) mice. Colorectal tumor incidences and multiplicities in Min/OPN(+/−) and Min/OPN(−/−) mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0.6 ± 0.8, 50% and 0.8 ± 0.9 vs. 80% and 1.6 ± 1.7, respectively. OPN expression in colorectal tumors was strongly upregulated in Min/OPN(+/+) compared to adjacent non-tumor parts, but was decreased in Min/OPN(+/−) and not detected in Min/OPN(−/−). Targets of OPN, matrix metalloproteinases (MMPs)-3, -9, and -13 were lowered by OPN deficiency. Macrophage marker F4/80 in colorectal tumors was also lowered by OPN deficiency. MMP-9 expression was observed in tumor cells and tumor-infiltrating neutrophils. These results indicate that induction of OPN by aberrant Wnt signaling could enhance colorectal tumor development in part by upregulation of MMP-3, -9, and -13 and infiltration of macrophage and neutrophils. Suppression of OPN expression could contribute to tumor prevention, but complete deficiency of OPN may cause some adverse effects. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessArticle Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice
Int. J. Mol. Sci. 2017, 18(4), 851; https://doi.org/10.3390/ijms18040851
Received: 10 March 2017 / Revised: 7 April 2017 / Accepted: 12 April 2017 / Published: 17 April 2017
Cited by 1 | PDF Full-text (2217 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and its inhibitor is reported to reduce cancer cell proliferation and induce apoptosis. Therefore, we asked whether acetazolamide, a CA
[...] Read more.
Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and its inhibitor is reported to reduce cancer cell proliferation and induce apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice, were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result, acetazolamide treatment reduced the total number of intestinal polyps by up to 50% compared to the control group. In addition, the acetazolamide-treated group had low cell proliferation and a high apoptosis ratio in the intestinal polyp epithelial cells. Moreover, the mRNA expression level of proinflammatory cytokines, such as IL-6, involved in the cell proliferation was decreased in the polyp part of the acetazolamide-treated group. Next, we examined the effects of acetazolamide on the activation of several transcriptional factors (AP-1, HIF, HSF, NF-κB, NRF2, p53, and STAT3) using a reporter gene assay in human colon cancer cells, Caco-2 cells. Among the examined transcriptional factors, NRF2 transcriptional activation was strongly induced. NRF2-targeting genes, γGCS, GPx1, HO-1, and NQO-1, were also elevated in the intestinal polyps of acetazolamide-treated Min mice. Our results suggested that CA is involved in intestinal carcinogenesis. Acetazolamide could inhibit polyp formation through suppressing local/general cytokine levels, i.e., IL-6, via NRF2 activation. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessArticle Preventive Effects of Heat-Killed Enterococcus faecalis Strain EC-12 on Mouse Intestinal Tumor Development
Int. J. Mol. Sci. 2017, 18(4), 826; https://doi.org/10.3390/ijms18040826
Received: 24 February 2017 / Revised: 7 April 2017 / Accepted: 9 April 2017 / Published: 13 April 2017
Cited by 3 | PDF Full-text (1091 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Establishing effective methods for preventing colorectal cancer by so-called “functional foods” is important because the global burden of colorectal cancer is increasing. Enterococcus faecalis strain EC-12 (EC-12), which belongs to the family of lactic acid bacteria, has been shown to exert pleiotropic effects,
[...] Read more.
Establishing effective methods for preventing colorectal cancer by so-called “functional foods” is important because the global burden of colorectal cancer is increasing. Enterococcus faecalis strain EC-12 (EC-12), which belongs to the family of lactic acid bacteria, has been shown to exert pleiotropic effects, such as anti-allergy and anti-infectious effects, on mammalian cells. In the present study, we aimed to evaluate the preventive effects of heat-killed EC-12 on intestinal carcinogenesis. We fed 5-week-old male and female Apc mutant Min mice diets containing 50 or 100 ppm heat-killed EC-12 for 8 weeks. In the 50 ppm treated group, there was 4.3% decrease in the number of polyps in males vs. 30.9% in females, and significant reduction was only achieved in the proximal small intestine of female mice. A similar reduction was observed in the 100 ppm treated group. Moreover, heat-killed EC-12 tended to reduce the levels of c-Myc and cyclin D1 mRNA expression in intestinal polyps. Next, we confirmed that heat-killed EC-12 suppressed the transcriptional activity of the T-cell factor/lymphoid enhancer factor, a transcriptional factor involved in cyclin D1 mRNA expression in intestinal polyps. Our results suggest that heat-killed EC-12 very weakly suppresses intestinal polyp development in Min mice, in part by attenuating β-catenin signaling, and this implies that heat-killed EC-12 could be used as a “functional food”. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessArticle Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
Int. J. Mol. Sci. 2017, 18(2), 413; https://doi.org/10.3390/ijms18020413
Received: 28 December 2016 / Revised: 19 January 2017 / Accepted: 10 February 2017 / Published: 15 February 2017
Cited by 4 | PDF Full-text (1097 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study
[...] Read more.
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessCommunication Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota
Int. J. Mol. Sci. 2016, 17(12), 2017; https://doi.org/10.3390/ijms17122017
Received: 27 October 2016 / Revised: 23 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
Cited by 11 | PDF Full-text (1474 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the
[...] Read more.
Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessArticle Different Susceptibilities between Apoe- and Ldlr-Deficient Mice to Inflammation-Associated Colorectal Carcinogenesis
Int. J. Mol. Sci. 2016, 17(11), 1806; https://doi.org/10.3390/ijms17111806
Received: 1 August 2016 / Revised: 21 September 2016 / Accepted: 19 October 2016 / Published: 28 October 2016
PDF Full-text (3034 KB) | HTML Full-text | XML Full-text
Abstract
Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC). However, the roles of apoliprotein (Apo) E (Apoe) and low-density lipoprotein (Ldl) receptor (Ldlr) in colorectal carcinogenesis have not
[...] Read more.
Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC). However, the roles of apoliprotein (Apo) E (Apoe) and low-density lipoprotein (Ldl) receptor (Ldlr) in colorectal carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of atherosclerosis to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. In Experiment 1, male Apoe-deficient (n = 20) and wild type (WT) mice (C57BL/6J, n = 21) were treated with a single intraperitoneal (i.p.) injection of AOM (10 mg/kg body weight) and then given 1.5% DSS in drinking water for seven days. They were maintained up to week 20 and sacrificed for the histopathological examination of colorectal tumors. The mRNA expression of cyclooxygenase (Cox)-2, inducible nitric oxide synthase (Nos2), tumor necrosis factor (Tnf)-α interleukin (Il)-1β, and Il-6 was assayed in the colorectal mucosa. In Experiment 2, male Ldlr-deficient (n = 14) and WT mice (C57BL/6J, n = 10) were given a single i.p. injection of AOM (10 mg/kg body weight) and then given 2% DSS in drinking water for seven days. They were sacrificed at week 20 to evaluate their colorectum histopathologically. In Experiment 1, the multiplicity of CRCs was significantly higher in the Apoe-deficient mice (2.75 ± 1.48) than in the WT mice (0.62 ± 0.67). The serum lipoprotein levels in the Apoe-deficient mice were also significantly higher than in the WT mice. In Experiment 2, the incidence (29%) and multiplicity (0.50 ± 0.94) of CRCs in the Ldlr mice were significantly lower than in the WT mice (80% incidence and 3.10 ± 2.38 multiplicity). The mRNA expression of two inducible enzymes and certain pro-inflammatory cytokines in the colorectum of each genotype was greater than in the respective WT mice. The values in the Apoe-deficient mice were much greater than in the Ldlr mice. These findings suggest that Apoe-deficient mice showed increased susceptibility to inflammation-associated colorectal carcinogenesis due to their high reactivity to inflammatory stimuli. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Review

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Open AccessReview Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond
Int. J. Mol. Sci. 2017, 18(8), 1699; https://doi.org/10.3390/ijms18081699
Received: 17 July 2017 / Revised: 31 July 2017 / Accepted: 31 July 2017 / Published: 3 August 2017
Cited by 7 | PDF Full-text (1972 KB) | HTML Full-text | XML Full-text
Abstract
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H.
[...] Read more.
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview Microbiota, Inflammation and Colorectal Cancer
Int. J. Mol. Sci. 2017, 18(6), 1310; https://doi.org/10.3390/ijms18061310
Received: 17 May 2017 / Revised: 14 June 2017 / Accepted: 15 June 2017 / Published: 20 June 2017
Cited by 14 | PDF Full-text (359 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the
[...] Read more.
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview p53 Expression as a Diagnostic Biomarker in Ulcerative Colitis-Associated Cancer
Int. J. Mol. Sci. 2017, 18(6), 1284; https://doi.org/10.3390/ijms18061284
Received: 27 April 2017 / Revised: 10 June 2017 / Accepted: 14 June 2017 / Published: 16 June 2017
Cited by 3 | PDF Full-text (3503 KB) | HTML Full-text | XML Full-text
Abstract
Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also known as colitic cancers) develop through the inflammation–dysplasia sequence, which is a major problem affecting the prognosis of patients with
[...] Read more.
Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also known as colitic cancers) develop through the inflammation–dysplasia sequence, which is a major problem affecting the prognosis of patients with UC. It is therefore very important to detect malignancy from UC at an early stage. As precancerous lesions arising in UC, there are pathological adenomatous changes, basal cell changes, in situ anaplasia, clear cell changes, and pan-cellular change. It is considered that the mutation of the p53 gene plays a crucial role, and the protein expression of p53 in dysplastic crypts may serve as a good biomarker in the early stages of UC-associated colon carcinogenesis. Immunohistochemistry for p53 is a very valuable diagnostic tool in UC-associated colon cancers. However, protein expression of p53 is not always universal, and additional methods may be required to assess p53 status in UC-associated colon cancers. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis
Int. J. Mol. Sci. 2017, 18(5), 918; https://doi.org/10.3390/ijms18050918
Received: 29 March 2017 / Revised: 20 April 2017 / Accepted: 21 April 2017 / Published: 27 April 2017
Cited by 1 | PDF Full-text (1588 KB) | HTML Full-text | XML Full-text
Abstract
The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are
[...] Read more.
The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species. The human vanin gene family consists of three genes: vanin-1, vanin-2 and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview Prevention of Colorectal Cancer by Targeting Obesity-Related Disorders and Inflammation
Int. J. Mol. Sci. 2017, 18(5), 908; https://doi.org/10.3390/ijms18050908
Received: 24 March 2017 / Revised: 17 April 2017 / Accepted: 20 April 2017 / Published: 26 April 2017
Cited by 2 | PDF Full-text (4154 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer is a major healthcare concern worldwide. Many experimental and clinical studies have been conducted to date to discover agents that help in the prevention of this disease. Chronic inflammation in colonic mucosa and obesity, and its related metabolic abnormalities, are considered
[...] Read more.
Colorectal cancer is a major healthcare concern worldwide. Many experimental and clinical studies have been conducted to date to discover agents that help in the prevention of this disease. Chronic inflammation in colonic mucosa and obesity, and its related metabolic abnormalities, are considered to increase the risk of colorectal cancer. Therefore, treatments targeting these factors might be a promising strategy to prevent the development of colorectal cancer. Among a number of functional foods, various phytochemicals, including tea catechins, which have anti-inflammatory and anti-obesity properties, and medicinal agents that ameliorate metabolic disorders, might also be beneficial in the prevention of colorectal cancer. In this review article, we summarize the strategies for preventing colorectal cancer by targeting obesity-related disorders and inflammation through nutraceutical and pharmaceutical approaches, and discuss the mechanisms of several phytochemicals and medicinal drugs used in basic and clinical research, especially focusing on the effects of green tea catechins. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction
Int. J. Mol. Sci. 2017, 18(4), 867; https://doi.org/10.3390/ijms18040867
Received: 31 March 2017 / Revised: 14 April 2017 / Accepted: 17 April 2017 / Published: 19 April 2017
Cited by 5 | PDF Full-text (2171 KB) | HTML Full-text | XML Full-text
Abstract
A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and
[...] Read more.
A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview The Five Immune Forces Impacting DNA-Based Cancer Immunotherapeutic Strategy
Int. J. Mol. Sci. 2017, 18(3), 650; https://doi.org/10.3390/ijms18030650
Received: 9 January 2017 / Revised: 6 March 2017 / Accepted: 13 March 2017 / Published: 17 March 2017
Cited by 2 | PDF Full-text (1579 KB) | HTML Full-text | XML Full-text
Abstract
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell
[...] Read more.
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, identification of neoantigens, mutanome studies, designing fusion plasmids, vaccine adjuvant modifications, and co-treatment with immune-checkpoint inhibitors. In this review, we follow a Porter’s analysis analogy, otherwise commonly used in business models, to analyze various immune-forces that determine the potential success and sustainable positive outcomes following DNA vaccination using non-viral tumor associated antigens in treatment against cancer. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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Open AccessReview Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets
Int. J. Mol. Sci. 2016, 17(11), 1958; https://doi.org/10.3390/ijms17111958
Received: 22 September 2016 / Revised: 1 November 2016 / Accepted: 16 November 2016 / Published: 23 November 2016
Cited by 4 | PDF Full-text (6646 KB) | HTML Full-text | XML Full-text
Abstract
Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review
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Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). These cells promote tumor growth by several mechanisms, including their inherent immunosuppressive activity, promotion of neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further enhanced by their cross-talk offering a myriad of potential anti-cancer therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid cells and give a general overview of their phenotypical and functional diversity, offering examples of possible therapeutic targets. Pharmacological targeting of inflammatory cells and molecular mediators may result in therapies improving patient condition and prognosis. Here, we review experimental and clinical findings on cancer-related inflammation with a major focus on creating an inventory of current small molecule-based therapeutic interventions targeting cancer-related inflammatory cells: TAMs and MDSCs. Full article
(This article belongs to the Special Issue Inflammation and Cancer) Printed Edition available
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