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Chitin or chitin-like glycans as targets for late-term cancer chemoprevention.

ABSTRACT: A consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant ?1-6 N-acetyl-d-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (?-1,4-linked N-acetyl-d-glucosamine) or a chitin-like polysaccharide (e.g., hyaluronan) may exist as a cancer-associated glycan, which can be targeted by the novel pyrimidine nucleotide derivative SP-1015 (designed as a chitin synthase inhibitor). Preliminary chemoprevention data of our group showed SP-1015 in the diet can inhibit benzo(a)pyrene-induced neoplasia in the forestomach of female A/J mice, and, of importance, this activity occurred at late stages in carcinogenesis. While no effect was seen in the murine lung, this may be due to the low bioavailability of the compound. A different route of administration (e.g. inhalation of an aerosol) may have potential to inhibit pulmonary carcinogenesis. We hypothesize that inhibitors of chitin or chitin-like glycan formation may be effective chemopreventive agents and suggest that further work is needed to study these novel targets for cancer prevention.

SUBMITTER: Wattenberg LW

PROVIDER: S-EPMC3058766 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Chitin or chitin-like glycans as targets for late-term cancer chemoprevention.

Wattenberg Lee W LW Patterson Steven S Antonides Jennifer D JD

Cancer prevention research (Philadelphia, Pa.) 20101201 12

A consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant β1-6 N-acetyl-d-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (β-1,4-linked N-acetyl-d-glucosamine) or a chitin-like polysaccharide (e.g., hyaluronan) may exist as a cancer-associated glycan, which c ...[more]

PMID: 21149328

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Project description:ImportanceLow-dose aspirin use for chemoprevention of lung cancer risk remains controversial.ObjectivesTo investigate the association between low-dose aspirin use and lung cancer risk, and to identify specific subgroups that may derive the most benefit from low-dose aspirin use.Design, setting, and participantsThis nationwide, retrospective, cohort study used data from the Korean National Health Information Database from 2002 to 2015. Data analyses were performed from October 2016 to December 2018. Eligible participants (n = 12 969 400) were people aged 40 to 84 years who had undergone national health screening between 2009 and 2010 and had no history of lung cancer between 2006 and 2010 and no standard-dose aspirin use for 6 months between 2002 and 2010.Main outcomes and measuresThe duration of low-dose aspirin use between January 2002 and December 2010 was calculated for each participant. Lung cancer was defined as the first recorded diagnosis of lung cancer-using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and expanding benefit coverage-between January 2011 and December 2015.ResultsA total of 63 040 participants with a mean (SD) age of 66.4 (9.3) years received a diagnosis of lung cancer. Of these, 45 156 (71.6%) were men. The incidence rate of lung cancer was 98.8 per 100 000 person-years. The duration of low-dose aspirin use was none for 10 987 417 participants (84.7%), 1 to 2 years for 750 992 participants (5.8%), 3 to 4 years for 506 945 participants (3.9%), 5 to 6 years for 371 062 participants (2.9%), 7 to 8 years for 240 528 participants (1.9%), and 9 years for 112 456 participants (0.9%). Compared with no aspirin use, 5 to 6 years (adjusted hazard ratio, 0.96 [95% CI, 0.92-0.99]), 7 to 8 years (adjusted hazard ratio, 0.94 [95% CI, 0.90-0.99]), and 9 years (adjusted hazard ratio, 0.89 [95% CI, 0.84-0.94]) of aspirin use were significantly associated with reduced lung cancer risk. After stratified analysis, a significant reduction of lung cancer risk was observed among people aged 65 years or older and among people without diabetes.Conclusions and relevanceAlthough the use of low-dose aspirin for more than 5 years was associated with decreased risk of lung cancer, particularly among elderly participants and among people without diabetes, the observed effect size was quite modest. Future prospective studies are needed to determine whether there is a causal association.

Dataset Information

Chitin or chitin-like glycans as targets for late-term cancer chemoprevention.

Publications

Chitin or chitin-like glycans as targets for late-term cancer chemoprevention.

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