Gastric cancer patient with c-MET amplification treated with crizotinib after failed multi-line treatment: A case report and literature review.

Gastric cancer is one of the most common gastrointestinal tumors. Most patients have been in advanced stage at diagnosis and lack effective treatment. Molecular targeted drugs have become new therapeutic strategies. MET is an important driving gene for the development of gastric cancer. MET gene amplification and protein over-expression are closely related to the invasion and metastasis, late stage and poor prognosis of gastric cancer. Crizotinib is a small molecule inhibitor against MET. There are few reports of crizotinib in gastric cancer patients with c-MET amplification. This article reports a case of c-MET gene amplification in advanced gastric cancer with liver metastases. After 2 months of treatment with crizotinib, liver lesions were completely relieved and progression-free survival lasted for up to 20 months.

Serum thrombospondin-2 is a candidate diagnosis biomarker for early non-small-cell lung cancer.

Thrombospondin-2 (THBS2) is a secreted protein overexpressed in numerous cancers and may function as a diagnostic tumor marker. The objective of the present study was to investigate the diagnostic performance of serum THBS2 in early stage non-small-cell lung cancer (NSCLC). Serum THBS2 and Cyfra21-1 level were evaluated in blood samples of 112 patients from NSCLC groups and 51 healthy control (HC) groups. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic significance. Serum THBS2 level was significantly up-regulated in NSCLC patients compared with healthy control subjects (P<0.0001), and the postoperative THBS2 level decreased significantly (P<0.0001). ROC curves analysis demonstrated that THBS2 was a comparable biomarker as Cyfra21-1 to distinguish early stage NSCLC or lung squamous cell carcinoma (SC) from healthy control subjects. And Cyfra21-1 was observed with significantly improved performances by the combination of THBS2 to distinguish early stage NSCLC (P<0.05) as well as SC (P<0.05) from the control subjects. In addition, THBS2 was estimated to perform well in the diagnosis of patients with Cyfra21-1-negative NSCLC (area under the curve [AUC] = 0.73). In summary, the present study suggested that serum THBS2 might be an early diagnostic biomarker for NSCLC.

Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis.

Cancer side-population (SP) represents a sub-population of stem-like cancer cells that have an important role in drug resistance due to their high expression of the ATP-binding cassette transporter ABCG2 involved in drug export. Auranofin (AF), a clinical drug of gold complex that is used in treatment of rheumatoid arthritis, has been reported inducing tumor antiproliferation. However, whether AF can impact SP cells remains unclear. Our study showed that AF caused a depletion of SP cells and a downregulation of stem cell markers, and impaired their ability to form tumor colonies in vitro and incidence to develop tumors in vivo of lung cancer cells. Reactive oxygen species (ROS) had an important role in mediating AF-induced depletion of SP cells, which could be reversed by antioxidant NAC. Further study revealed that AF could also cause ATP depletion by inhibition of glycolysis. The depletion of cellular ATP might impair the function of ABCG2 pump, leading to increased drug accumulation within the cells and thus enhancing anticancer activity of chemotherapeutic agents such as adriamycin. Synergistic effect of AF and adriamycin was demonstrated both in vitro and in vivo. Simultaneous increase of ROS and inhibition of glycolysis is a novel strategy to eliminate stem-like cancer cells. Combination of AF with adriamycin seems to be promising to enhance therapeutic effectiveness.

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter.

DNA topoisomerases are essential to modulate DNA topology during various cellular genetic processes. The expression and distinct prognostic value of topoisomerase isoforms in non-small-cell lung cancer (NSCLC) is not well established. In the current study, we have examined the mRNA expression of topoisomerase isoforms by using Oncomine analysis and investigated their prognostic value via the Kaplan-Meier plotter database in NSCLC patients. Our analysis indicated that the expression level of topoisomerases in lung cancer was higher compared with normal tissues. Especially, high expression of two topoisomerase isoforms, TOP2A and TOP3A, was found to be correlated to worse overall survival (OS) in all NSCLC and lung adenocarcinoma (Ade) patients, but not in lung squamous cell carcinoma (SCC) patients. In a contrast, high expression of isoforms TOP1 and TOP2B indicated better OS in all NSCLC and Ade, but not in SCC patients. Meanwhile, high expression of TOP1MT and TOP3B was not correlated with OS in NSCLC patients. Furthermore, we also demonstrated a relationship between topoisomerase isoforms and the clinicopathological features for the NSCLC patients, such as grades, clinical stages, lymph node status, smoking status, gender, chemotherapy and radiotherapy. These results support that TOP2A and TOP3A are associated with worse prognosis in NSCLC patients. In addition, our study also shows that TOP1 and TOP2B contribute to favorable prognosis in NSCLC patients. The exact prognostic significance of TOP1MT and TOP3B need to be further elucidated. Comprehensive evaluation of expression and prognosis of topoisomerase isoforms will be a benefit for the better understanding of heterogeneity and complexity in the molecular biology of NSCLC, paving a way for more accurate prediction of prognosis and discovery of potential drug targets for NSCLC patients.

Protective effect of antioxidant on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.

OBJECTIVES: To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer. METHODS: Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model. The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM (1 mg/kg·0.2 mL/2 d). The model control group received normal saline (NS) of the same volume at the same time. 1% TBHQ was added into the diet of mice of the antioxidant intervention group. Seven weeks later, morning urines and peripheral blood were randomly collected to detect UAlb, UCr, BUN, Scr and UAlb/Cr levels. All mice were beheaded. The renal tissues were made into homogenate, and SOD, T-AOC and MDA content in tissues were detected followed by cell lysis. All data were processed using SPSS19.0. RESULTS: The UAlb/Cr, BUN, Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD, T-AOC in doxorubicin chemotherapy group were lower than those of model control group (P < 0.01). The UAlb/Cr, BUN, Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD, T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group (P < 0.05). The BUN of model control group was higher than that of blank group, and T-AOC was lower than that of blank group, and difference was statistically significant (P < 0.05). CONCLUSIONS: Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer. TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.