Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine

Abstract

Apoptosis has been described as an energy-consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynamic positron emission tomography (PET) measurements of fluorine-18 fluorodeoxyglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to and after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measurements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determined using the TUNEL reaction. In vivo an increase in FDG transport and phosphorylation occurred early after gemcitabine treatment, although TdR incorporation into the DNA of the tumours declined. In vitro, an enhanced glucose transport, an increase in TdR uptake in the cytoplasm and a decrease in TdR incorporation in the nucleic acid fraction early after treatment occurred. Inhibition of glucose transport caused an increase in the amount of apoptotic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytotoxic drugs like gemcitabine.

In vivo imaging of apoptosis

“…89 However, because apoptosis must use energy, at least initially, glucose demand may increase temporarily in some clinical situations. 90 One example appears to be the "metabolic flare" often observed on 18 F-FDG PET images after hormonal therapy administrated for estrogen receptor-positive human breast cancer. 91 The metabolic flare is this select patient population may also be a useful indicator of responsiveness to anti-estrogen therapy as opposed to non-hormonal chemotherapy.…”

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…In several pre-clinical studies gemcitabine demonstrated strong antitumor effects on HCC (29)(30)(31). Therefore, based on pre-clinical rationale gemcitabine was evaluated in patients with advanced HCC.…”

Feasibility of 18F-FDG PET as a Noninvasive Diagnostic Tool of Muscle Denervation: A Preliminary Study

“…Another possible hypothesis is apoptotic reaction in denervated skeletal muscles. Apoptosis has been considered as an energy-consuming process that can be accompanied by an 18 F-FDG uptake increase (10). There were several previous studies that have demonstrated that muscle denervation stimulates mitochondrially mediated apoptosis (11).…”