Nucleoside-catabolizing Enzymes in Mycoplasma-infected Tumor Cell Cultures Compromise the Cytostatic Activity of the Anticancer Drug Gemcitabine

Abstract

Background: Gemcitabine is used to treat solid tumors. Some mycoplasmas preferentially colonize tumors in patients. Results: Mycoplasma-encoded cytidine deaminase and pyrimidine nucleoside phosphorylase compromise the cytostatic/antitumor activity of gemcitabine in mycoplasma-infected tumor cell cultures and xenografts in mice. Conclusion: Tumor-associated mycoplasmas may decrease the therapeutic efficiency of gemcitabine. Significance: Current treatment of mycoplasma-infected tumors with gemcitabine may be suboptimal.

Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

“…This experiment revealed that conditioned medium from M. hyorhinis -infected HDFs metabolizes gemcitabine into its deaminated inactive metabolite 2′,2′-difluorodeoxyuridine (7) as has been previously reported (8, 9) (Fig. 1C and fig.…”

“…To find the bacterial genes involved in gemcitabine resistance, we first considered the bacterial enzyme cytidine deaminase (CDD) because it was previously shown to mediate gemcitabine deamination by Mycoplasma (8). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) (10), of 2,674 bacterial species analyzed, 11.4% contained an ∼880-nucleotide long form of CDD (CDD L ), 44.4% contained a ∼400-nucleotide short form (CDD S ), and 44.2% lacked CDD entirely (Fig.…”

Bacterial snack attack deactivates a drug

“…The cytidine deaminase enzyme of M. hyorhinis might be responsible for converting gemcitabine into an inactive form through a metabolic process called deamination 8 .…”

“…Such optimization has conventionally been achieved either by testing combinations of variables manually or by using machinelearning techniques. Each of these approaches has advantages in different situations and both were instrumental in the discovery of the Higgs boson 7,8 in 2012.…”

50 & 100 Years Ago

“…Such optimization has conventionally been achieved either by testing combinations of variables manually or by using machinelearning techniques. Each of these approaches has advantages in different situations and both were instrumental in the discovery of the Higgs boson 7,8 in 2012. Human-constructed classifiers often have a physically intuitive meaning and can be optimized using a relatively small amount of data.…”