FLS leads to high survival rates and low neurological morbidity for fetuses in TTTS. FLS is an effective therapeutic option for TTTS before 26 weeks of gestation. Preoperative Doppler findings of the umbilical artery and the ductus venosus are useful in predicting prognosis following FLS.
This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.
Bile duct necrosis because of transcatheter hepatic arterial embolization (THAE) in two patients with hepatocellular carcinoma is reported. Preoperative THAE was performed on 29 patients, and bile duct necrosis was experienced by two of the 29 (7%). In these two patients, gelatin (Gelfoam) powder was used as the embolus. Among the 24 whose embolus was clear, four were embolized with gelatin powder. Therefore, incidence of bile duct necrosis after THAE with gelatin powder was 50%. Because of the hazards of severe complications such as bile duct necrosis, we conclude that gelatin powder should not be used except for the THAE of no more than one segment of the liver.
A previous dose-escalation study of sulfasalazine (SSZ), an inhibitor of cystine-glutamate exchange transporter xc (-), in the variant form of CD44 (CD44v)-positive cancer stem cells (CSCs) suggested that administration of SSZ induces the reduction of CD44v-positive cells and intracellular reduced glutathione (GSH) levels in patients with advanced gastric cancer (AGC). Here we report a study to evaluate SSZ in combination with cisplatin in patients with CD44v-expressing AGC refractory to cisplatin. SSZ was given by oral administration four times daily with 2 weeks on and 1 week off. Cisplatin at 60 mg/m was administered every 3 weeks. Of the 15 patients who underwent prescreening of CD44v expression, 8 patients were positive, and 7 patients were treated with the dose level of SSZ at 6 g/day. One patient experienced dose-limiting toxicity (DLT) as grade 3 anorexia. Although no other patients experienced DLT, 4 patients required dose interruption or reduction of SSZ; thus, we terminated further dose escalation. No patient achieved objective response, but 1 patient completed six cycles with stable disease for more than 4 months as well as reduction of intratumoral GSH level. The combination of SSZ plus cisplatin was manageable, although dose modification was frequently required during a short observational period.
GBS‐01, an extract from the fruit of Arctium lappa L. is an orally administered drug rich in arctigenin, which has been reported to exert antitumor activity by attenuating the tolerance of cancer cells to glucose deprivation. We investigated the maximum tolerated dose of GBS‐01 based on the frequency of the dose‐limiting toxicities (DLTs) and pharmacokinetics in patients with advanced pancreatic cancer refractory to gemcitabine. GBS‐01 was given orally at escalating doses from 3.0 g (containing 1.0 g burdock fruit extract) to 12.0 g q.d. A DLT was defined as a grade 4 hematological toxicity and grade 3 or 4 non‐hematological toxicity appearing during the first 28 days of treatment. Fifteen patients (GBS‐01 dose level 1 [3.0 g], three patients; dose level 2 [7.5 g], three patients; and dose level 3 [12.0 g], nine patients) were enrolled. None of the patients at any of the three dose levels showed any sign of DLTs. The main adverse events were increased serum γ‐glutamyl transpeptidase, hyperglycemia, and increased serum total bilirubin; however, all the toxicities were mild. Of the 15 patients, 1 showed confirmed partial response and 4 patients had stable disease. The median progression‐free and overall survival of the patients were 1.1 and 5.7 months, respectively. The pharmacokinetic study revealed a high bioavailability of arctigenin and rapid conjugation of the drug with glucuronic acid. The recommended dose of GBS‐01 was 12.0 g q.d, and favorable clinical responses were obtained. This trial was registered at UMIN‐CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number UMIN000005787.
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