Inflammation and the development of pancreatic cancer.
Farrow B, Evers BM.
Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard,
77555, Galveston, TX, USA
Objective. Pancreatic cancer has an extremely poor prognosis and the cellular mechanisms
contributing to pancreatic cancer are relatively unknown. The goals of this review are to present
the epidemiological and experimental data that supports inflammation as a key mediator of
pancreatic cancer development, to explain how inflammatory pathways may create an
environment that supports tumor formation, and to discuss how the use of novel agents directed
at these pathways may be used for the treatment of pancreatic malignancy. Summary
Background Data. Inflammation has been identified as a significant factor in the development of
other solid tumor malignancies. Both hereditary and sporadic forms of chronic pancreatitis are
associated with an increased risk of developing pancreatic cancer. The combined increase in
genomic damage and cellular proliferation, both of which are seen with inflammation, strongly
favors malignant transformation of pancreatic cells. Cytokines, reactive oxygen species, and
mediators of the inflammatory pathway (e.g., NF-kappaB and COX-2) have been shown to
increase cell cycling, cause loss of tumor suppressor function, and stimulate oncogene expression;
all of which may lead to pancreatic malignancy. Anti-cytokine vaccines, inhibitors of
pro-inflammatory NF-kappaB and COX-2 pathways, thiazolidinediones, and anti-oxidants are
potentially useful for the prevention or treatment of pancreatic cancer. Redirection of
experimental interests toward pancreatic inflammation and mechanisms of carcinogenesis may
identify other novel anti-inflammatory agents or other ways to screen for or prevent pancreatic
cancer. Conclusion. Pancreatic inflammation, mediated by cytokines, reactive oxygen species,
and upregulated pro-inflammatory pathways, may play a key role in the early development of
pancreatic malignancy.
Some abstracts are presented which suggest some link between cancer and inflammation among other things.
AUTHOR:
Jaiswal M, LaRusso NF, Gores GJ
TITLE:
Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to
oncogenesis.
SOURCE:
Am J Physiol Gastrointest Liver Physiol; 281(3):G626-34 2001 UI: 21409758
ABSTRACT:
Chronic inflammation of gastrointestinal tissues is a well-recognized risk factor for the
development of epithelial cell-derived malignancies. Although the inflammatory mediators
linking chronic inflammation to carcinogenesis are numerous, current information suggests that
nitric oxide (NO) contributes to carcinogenesis during chronic inflammation. Inducible nitric
oxide synthase (iNOS), expressed by both macrophages and epithelial cells during
inflammation, generates the bioreactive molecule NO. In addition to causing DNA lesions,
NO can directly interact with proteins by nitrosylation and nitosation reactions. The
consequences of protein damage by NO appear to be procarcinogenic. For example, NO
inhibits DNA repair enzymes such as human 8-oxodeoxyguanosine DNA glycosylase 1 and
blocks apoptosis via nitrosylation of caspases. These cellular events permit DNA damage to
accumulate, which is required for the numerous mutations necessary for development of
invasive cancer. NO also promotes cancer progression by functioning as an angiogenesis
factor. Strategies to inhibit NO generation during chronic inflammation or to scavenge reactive
nitrogen species may prove useful in decreasing the risk of cancer development in chronic
inflammatory gastrointestinal diseases.
link for abstract
AUTHOR:
O'Byrne KJ, Dalgleish AG
TITLE:
Chronic immune activation and inflammation as the cause of malignancy.
SOURCE:
Br J Cancer; 85(4):473-83 2001 UI: 21397875
ABSTRACT:
Several chronic infections known to be associated with malignancy have established
oncogenic properties. However the existence of chronic inflammatory conditions that do not
have an established infective cause and are associated with the development of tumours
strongly suggests that the inflammatory process itself provides the prerequisite environment
for the development of malignancy. This environment includes upregulation of mediators of
the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of
inflammatory cytokines and prostaglandins which themselves may suppress cell mediated
immune responses and promote angiogenesis. These factors may also impact on cell growth
and survival signalling pathways resulting in induction of cell proliferation and inhibition of
apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen
species and metabolites such as malondialdehyde within the affected cells that may in turn
induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed
that the conditions provided by a chronic inflammatory environment are so essential for the
progression of the neoplastic process that therapeutic intervention aimed at inhibiting
inflammation, reducing angiogenesis and stimulating cell mediated immune responses may
have a major role in reducing the incidence of common cancers.
Record 5
AUTHOR:
Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS
TITLE:
Molecular mechanisms underlying chemopreventive activities of anti-inflammatory
phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B
activation.
SOURCE:
Mutat Res; 480-481:243-68 2001 UI: 21398740
ABSTRACT:
A wide array of phenolic substances, particularly those present in edible and medicinal plants,
have been reported to possess substantial anticarcinogenic and antimutagenic activities. The
majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties
which appear to contribute to their chemopreventive or chemoprotective activity.
Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important
enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or
iNOS has been associated with pathophysiology of certain types of human cancers as well as
inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances
with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on
carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment
of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin
gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress
tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor
nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS
expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and
iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling
evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated
protein kinase are key elements of the intracellular signaling cascades responsible for
NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and
resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible
mechanisms underlying inhibition of NF-kappa B activation by aforementioned
phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha,
which hampers subsequent nuclear translocation of the functionally active subunit of
NF-kappa B.link click herehe effect of Sambucol, a black elderberry-based, natural product, on the production of
human cytokines: I. Inflammatory cytokines.
SOURCE:
Eur Cytokine Netw; 12(2):290-6 2001 UI: 21292762
ABSTRACT:
Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry
extract. They are natural remedies with antiviral properties, especially against different strains
of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza
virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the
duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody
level to influenza virus in the Sambucol group, than in the control group. The present study
aimed to assess the effect of Sambucol products on the healthy immune system - namely, its
effect on cytokine production. The production of inflammatory cytokines was tested using
blood - derived monocytes from 12 healthy human donors. Adherent monocytes were
separated from PBL and incubated with different Sambucol preparations i.e., Sambucol
Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and
Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6,
IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45
fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking
increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that,
in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations
activate the healthy immune system by increasing inflammatory cytokine production.
Sambucol might therefore be beneficial to the immune system activation and in the
inflammatory process in healthy individuals or in patients with various diseases. Sambucol
could also have an immunoprotective or immunostimulatory effect when administered to
cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view
of the increasing popularity of botanical supplements, such studies and investigations in vitro,
in vivo and in clinical trials need to be developed.
MESH TERMS:
Angiosperms/*Chemistryclick for link
CANCERLIT® Detailed Search Results
Record 1
AUTHOR:
Hsieh CL, Yen GC
TITLE:
Antioxidant actions of du-zhong (Eucommia ulmoides Oliv.) toward oxidative damage in
biomolecules.
SOURCE:
Life Sci; 66(15):1387-400 2000 UI: 21079221
ABSTRACT:
This study aimed to investigate the antioxidant effect of water extracts of Du-zhong (WEDZ)
on oxidative damage in biomolecules such as deoxyribose, DNA, and 2'-deoxyguanosine
(2'-dG) as induced by Fenton reaction. The WEDZ used included leaves, raw cortex, and
roasted cortex. All of the WEDZ inhibited the oxidation of deoxyribose induced by
Fe(3+)-EDTA/H2O2/ascorbic acid in a concentration dependent manner. At a
concentration of 1.14 mg/mL, the inhibitory effect of the extracts of leaves, roasted cortex,
and raw cortex was 85.2%, 68.0% and 49.3%, respectively. The extract of leaves inhibited
the strand-breaking of DNA induced by the Fenton reaction at concentrations of 5 and 10
micrograms/microL. This inhibitory effect was similar to mannitol whereas the extracts of raw
cortex and roasted cortex had no inhibitory effect at all. WEDZ also inhibited the oxidation of
2'-dG to 8-OH-2'-dG induced by Fe(3+)-EDTA/H2O2/ascorbic acid. Gallic acid had a
prooxidant effect, but trolox and mannitol had an antioxidant effect. The leaf extract had a
marked inhibitory effect on Fenton reaction induced oxidative damage in biomolecules. The
extract of roasted cortex exhibited modest inhibition while the extract of raw cortex had the
least inhibitory effect on oxidative damage in biomolecules. This is in contrast to gallic acid in
the same reaction system, whose higher reducing power and weaker chelating ability may
contribute to its prooxidant effect. In the present study, leaf extract of Du-zhong had
inhibitory effect on oxidative damage in biomolecules. Therefore, drinking of Du-zhong tea
(leaf extract) over a long period of time may have antica