Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Objectives The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. Methods The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). Results There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. Conclusion TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable (AU)

Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. METHODS: The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. CONCLUSION: TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.

SOX combined with intraperitoneal perfusion of docetaxel compared with DOS regimen in the first-line therapy for advanced gastric cancer with malignant ascites: a prospective observation.

OBJECTIVE: This study aimed to verify the survival superiority of the combination of intraperitoneal perfusion and systemic chemotherapy over standard systemic chemotherapy. METHODS: A total of 78 advanced gastric cancer patients with malignant ascites were randomly divided into D-SOX group (intraperitoneal infusion of docetaxel 30 mg/m2 on d1 and d8, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14) and DOS group (intravenous docetaxel 60 mg/m2 on d1, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14). Efficacy of both groups was evaluated every 2 cycles with 21 days as a cycle. The primary endpoint was overall survival, and the secondary endpoints were objective response rate, ascites control rate, negative conversion rate of ascites cytology, and side effects. RESULTS: The median overall survival in D-SOX group was significantly higher than that in the DOS group (11.7 vs 10.3 months, HR 0.52, 95%CI 0.31-0.86, P = 0.005). The ascites control rate in the D-SOX group was 58.9% and 30.8% in DOS group (95%CI 42.8-75.1% vs 95%CI 15.6-45.9%, P = 0.012). Besides, the adverse reactions were tolerable in both groups, and patients in the D-SOX group had lower grade 3/4 blood toxicity than that in the DOS group (26% vs 54%, P = 0.01). CONCLUSION: Compared with traditional systemic chemotherapy, docetaxel intraperitoneal infusion combined with chemotherapy has better therapeutic effect on gastric cancer ascites, with better survival benefit and tolerance and less hematological toxicity, which is worthy of further research and clinical application.

The expression of Slit2 and Robo1 increased during retinoic acid syndrome in acute promyelocytic leukemia and impacted differentiated cell migration.

Retinoic acid syndrome (RAS) is a serious complication developed during the induction therapy of acute promyelocytic leukemia (APL). Cytokines and differentiated cells migration play important roles in the development of RAS. Slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) involve in cell migration. Our study aimed to investigate the expression of Slit2 and Robo1 in APL and check whether they affected promyelocytes migration. 62 cases of newly diagnosed APL patients were involved and received all-trans retinoic acid (ATRA) and arsenic trioxide as induction therapy. Bone marrow cells (BMCs) were obtained on days 0 and 28, and promyelocytes and plasma were collected from day 1 to day 21. The expression of Robo1 in promyelocytes, and that of Slit2 and cytokines, including IL-8,IL-1ß and others, in serum were monitored. 20 healthy individuals donated their cells as control. Of the 62 APL patients, 16 (25.81%) patients developed RAS. The expression of Robo1, Slit2 and IL-8 increased significantly with the development of RAS. In the 16 patients with RAS, levels of Slit2, Robo1 and IL-8 were higher during the development of RAS than before or after the RAS (P < 0.05). RhSlit2-N and rhIL-8 induced cells migration, and the migration induced by IL-8 was not inhibited by rhSlit2-N. Elevated Slit2 and Robo1 levels might be useful markers for the diagnosis and treatment of RAS. The levels of Slit2, Robo1 and IL-8 showed a positive correlation with the severity of RAS. Slit2 and IL-8 promoted the migration of differentiated cells.

Erratum: Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells.

[This corrects the article on p. 1295 in vol. 10, PMID: 29887946.].

Erratum: Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells.

[This corrects the article on p. 1295 in vol. 10, PMID: 29887946.].

Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells.

BACKGROUND: Recent studies have reported that an elevated intracellular glutathione (GSH) level is associated with resistance of non-small cell lung cancer (NSCLC) cell lines to cisplatin (CDDP). It is well-known that GSH is widely used in the clinic as a hepatoprotective agent. However, whether exogenous GSH can affect the sensitivity of NSCLC cells to CDDP remains unclear. The aim of this study is to evaluate the role of exogenous GSH in the resistance of A549 cells to CDDP. METHODS: The effect of GSH and CDDP on the proliferation of A549 cells was analyzed by MTT assay. Subsequent experiments were conducted in A549 cells divided into four groups: control group (untreated cells), GSH group (treated with 120 µg/ml GSH for 48 h), CDDP group (treated with 10 µg/ml CDDP for 48 h) and CDDP+GSH group (treated with 10 µg/ml CDDP+120 µg/ml GSH for 48 h). Apoptosis was detected by flow cytometry. Light microscopy, fluorescence microscopy and electron microscopy were performed to study morphologic and ultrastructural differences among the four groups of cells. Intracellular GSH level and γ-GCS expression were determined by immunohistochemistry (IHC). Cellular platinum uptake was assessed by inductively coupled plasma mass spectrometry (ICP-MS). Quantitative RT-PCR analysis was performed to measure the expression of caspase3, caspase9, bax, bcl-2 and MDR-1. Western blot analysis was conducted to examine the protein levels of GST-π, MRP-1 and P-gp. RESULTS: Growth inhibition and apoptosis were reduced in A549 cells in the CDDP+GSH group compared to those in the CDDP group 48 h post-treatment. Alterations in cellular morphology and ultrastructure, as well as typical characteristics of apoptosis, were observed. Intracellular GSH and γ-GCS levels were elevated by exogenous administration of GSH; in contrast, cellular platinum concentration fell rapidly. Relative to the CDDP group, the CDDP+GSH group exhibited 47.92%, 47.82% and 63.75% downregulation in caspase3, caspase9 and bax mRNA expression, respectively, and a 2.17-fold increase in bcl-2 mRNA level. In addition, there were 1.58-fold and 2.67-fold increases in the level of GST-π and MRP-1, respectively; however, the changes in MDR-1 and P-gp levels were not statistically significant. CONCLUSIONS: Our data demonstrated that exogenous GSH used as hepatinica in the clinic could induce resistance of A549 cells to CDDP by inhibiting apoptosis, elevating cellular GSH levels, inactivating the mitochondria-mediated signaling pathway, and increasing the expression of GST-π, γ-GCS and MRP1 to increase CDDP efflux.

Serum immunoreactivity of SMP30 and its tissues expression in hepatocellular carcinoma.

OBJECTIVES: To detect serum antibody against SMP30 in HCC patients and to evaluate its potential associations with HCC patient's clinical parameter and expression levels in HCC tissues. DESIGN AND METHODS: Serum antibody to SMP30 was tested by ELISA method; SMP30 mRNA and protein expression in HCC patients were analyzed using the methods of in situ nucleic acid hybridization and immunohistochemistry, respectively. RESULTS: The highest relevance of SMP30 antibody was associated with HCC (32.4%). The positive rate of SMP30 antibody was not related to the age of patients, tumor size, metastasis and infections of HBV, but the positive rate for SMP30 antibody in the HCC sera with alpha-fetoprotein (AFP) negative was higher (43.6%) compared with that AFP positive (26.2%). Both SMP30 mRNA and protein expression levels were downregulated in HCC and upregulated in adjacent tissues. CONCLUSIONS: SMP30 may be useful for HCC serologic screening, especially for the patients with AFP negative.

Identification of HCC-22-5 tumor-associated antigen and antibody response in patients.

BACKGROUND: Serological identification of antigens by recombinant expression cloning (SEREX) is a promising method used to analyze tumor-associated antigen (TAA). Nineteen primary HCC-associated antigens have been found from a HCC cDNA library using autogenous serum by the SEREX approach. We searched for HCC-associated antigens and applied them to HCC diagnosis. METHODS: Nine of 19 primaries HCC-associated antigens identified by SEREX method were tested their immune response again with distinct allogeneic sera. One of the screened HCC-associated antigens, HCC-22-5 was recombined and expressed and made the frequency analysis of its seropositivity in various patients using the methods of Western-blot and ELISA. RESULTS: SEREX analysis showed that 9 primary HCC-associated antigens had high-titered IgG antibody in the majority of HCC patients. Western-Blot method confirmed that 3/7 HCC patients had antibodies against HCC-22-5, which demonstrated that expressed HCC-22-5 antigen had the character of antigen. Sera samples from 341 patients and 80 normal individuals have been tested for autoantibodies against HCC-22-5 by ELISA method. The results found that 51/128 of HCC, 11/76 of chronic hepatitis, 11/22 of liver cirrhosis and 8/54 of nasopharynx cancer patients had antibodies against HCC-22-5. No antibody response to HCC-22-5 had been found in the sera of 7 lung cancers, 54 gastric-intestine patients and 80 normal individuals. The groups of HCC and liver cirrhosis had higher antibody positive rate than that of other groups (p<0.05). In the HCC sera with alpha-fetoprotein (AFP) negative, the positive rate of HCC-22-5 was as high as 78.9%. CONCLUSIONS: HCC-22-5 can be used for HCC serologic screening, especially for the patients with AFP negative.