Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

BACKGROUND: Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. METHODS: A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. RESULTS: Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. CONCLUSIONS: At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.

Cost-effectiveness analysis of selexipag for the combined treatment of pulmonary arterial hypertension.

Objective: Adding selexipag to the combined treatment of endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitor (PDE5i) reduces the risk of clinical worsening events in patients with pulmonary arterial hypertension (PAH) but at a considerably higher cost. This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of ERA and PDE5i in patients with PAH from a Chinese healthcare system perspective. Methods: A Markov model was developed to assess costs and quality-adjusted life years (QALYs) of macitentan + tadalafil + selexipag vs. macitentan + tadalafil for the treatment of PAH. Markov states included WHO Functional Class (FC) (I-IV) and death. Transition probabilities were based on data from the TRITON trial. Mortality rates, costs, and utilities were obtained from published literature and public databases. Results: In the base case analysis, compared with macitentan + tadalafil, selexipag + macitentan + tadalafil increased costs ($357,807.588 vs. $116,534.543, respectively) and QALYs (7.234 QALYs vs. 6.666 QALYs, respectively). The resulting incremental cost-effectiveness ratio was $424,746.070 per QALY, which was higher than the willingness-to-pay (WTP) of $38,223.339 per QALY. The results were most sensitive to HR for mortality of patients with FC IV relative to the general population, discount rate, and the cost of selexipag. The probability was greater than 50% for the selexipag + macitentan + tadalafil only if the WTP was more significant than $426,019.200 per QALY. Conclusion: In China, adding selexipag may not be cost-effective for patients with PAH who failed to control their condition after combined treatment of ERA and PDE5i. Results of the analysis can aid discussions on the value and position of selexipag for the combined treatment of PAH.

Sauchinone prevents TGF-ß-induced EMT and metastasis in gastric cancer cells.

Sauchinone, one of the active lignan isolated from the roots of Saururus chinensis, was reported to possess diverse pharmacological properties, such as hepatoprotective, anti-inflammatory and anti-tumor effects. However, the possible role of sauchinone in the epithelial-mesenchymal transition (EMT) remains unclear. Thus, the aim of this study was to investigate the effect of sauchinone on the EMT in gastric cancer cells. Our results demonstrated that sauchinone significantly inhibited transforming growth factor-ß1 (TGF-ß1)-induced migration and invasion in gastric cancer cells. In addition, sauchinone efficiently suppressed TGF-ß1-induced EMT process in gastric cancer cells. Furthermore, pretreatment with sauchinone dramatically inhibited the activation of PI3K/Akt and Smad2/3 signaling pathways in TGF-ß1-stimulated gastric cancer cells. In conclusion, our findings revealed that sauchinone inhibits the TGF-ß1-induced EMT in gastric cancer cells via down-regulation of PI3K/Akt and Smad2/3 signaling pathways. Thus, sauchinone may be a therapeutic agent for treatment of gastric cancer.

Retracted Article: Daphnetin inhibits proliferation and glycolysis in colorectal cancer cells by regulating the PI3K/Akt signaling pathway.

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities. However, the effects of daphnetin on cell proliferation, migration, and glucose metabolism in colorectal cancer (CRC) cells remains unknown. In this study, the effects of daphnetin on CRC cell proliferation, migration, and glucose metabolism have been examined. The results showed that daphnetin inhibited the proliferation, migration, and invasion of CRC cells, and induced CRC cell apoptosis. Furthermore, daphnetin suppressed intracellular glucose and lactate production, and downregulated the expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) in CRC cells. Furthermore, daphnetin prevented activation of the PI3K/Akt pathway in CRC cells. These findings demonstrated that daphnetin inhibited the proliferation, migration and glucose metabolism in CRC cells by suppressing the PI3K/Akt signaling pathway. Therefore, daphnetin has potential as a novel anticancer agent for CRC treatment.

AQP5 promotes hepatocellular carcinoma metastasis via NF-κB-regulated epithelial-mesenchymal transition.

Aquaporin 5 (AQP5), a transmembrane protein, is known for its involvement in the progress of many diseases such as chronic kidney disease and systemic disease. Recently, AQP5 has been reported to play an important role in cancer progression. However, little is known about its precise functions in hepatocellular carcinoma (HCC). This study aimed to investigate the specific role of AQP5 in HCC. The results showed that AQP5 was highly expressed in HCC cell lines and its down-regulation inhibited HCC cell invasion and tumor metastasis in vitro and in vivo. In addition, down-regulation of AQP5 suppressed the epithelial-mesenchymal transition (EMT) process in HCC cells by modulating EMT-related molecules such as E-cadherin, α-catenin, N-cadherin and Vimentin. Further studies on corresponding mechanisms indicated that AQP5 down-regulation inhibited HCC metastasis and EMT partly via inactivation of the NF-κB signaling pathway. Taken together, these findings suggest that AQP5 may be a potential therapeutic target for HCC.