Phase II Study of a Bi-Weekly Chemotherapy Regimen of Combined Liposomal Paclitaxel and Nedaplatin for the Treatment of Advanced Squamous Cell Lung Cancer.

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8-9.2). The median survival time was 16 months (95% confidence interval: 14.1-17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.

Exosome-Mediated Transfer of lncRNA HOTTIP Promotes Cisplatin Resistance in Gastric Cancer Cells by Regulating HMGA1/miR-218 Axis.

BACKGROUND: Chemoresistance has become a major obstacle for cancer therapy in clinic. Long noncoding RNAs (lncRNAs) have been reported to play critical roles in the development of chemoresistance in various tumors, including gastric cancer (GC). However, the role of HOXA transcript at the distal tip (HOTTIP) within extracellular vesicles (exosomes) in cisplatin-resistant GC cells remains largely unknown. MATERIALS AND METHODS: Cell proliferation, migration and invasion were detected using Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Western blot assay was employed to analyze the protein levels of E-cadherin, N-cadherin, Vimentin, CD63, CD83, GRP78, HMGA1, and high-mobility group A1 (HMGA1). The expression levels of HOTTIP, microRNA-218 (miR-218) and HMGA1were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-218 and HOTTIP or HMGA1 was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted in cisplatin-resistant GC cells. HOTTIP level was upregulated in cisplatin-resistant GC cells and its downregulation enhanced cisplatin sensitivity. Moreover, extracellular HOTTIP could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating cisplatin resistance. Additionally, exosomal HOTTIP promoted cisplatin resistance via activating HMGA1 in GC cells. Interestingly, HMGA1 was a target of miR-218 and miR-218 could directly bind to HOTTIP. Clinically, high expression of exosomal HOTTIP in serum was associated with poor response to cisplatin treatment in GC patients. CONCLUSION: Exosomal HOTTIP contributed to cisplatin resistance in GC cells by regulating miR-218/HMGA1 axis, providing a novel avenue for the treatment of GC.

RETRACTED: Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "…the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editors-in-Chief decided to retract the article.

The prognostic significance of FBXO2 expression in colorectal cancer.

Colorectal cancer is the third most frequently diagnosed malignancy, and the prognosis at advanced tumor stages remains poor. FBXO2, a member of the F-box protein family, is a cytoplasmic protein and an ubiquitin ligase. The aim of this study was to investigate the role of FBXO2 in colorectal cancer. The expression levels of Ki67, N-cadherin and FBXO2 were detected in 195 pairs of primary CRC tissues using immunohistochemistry (IHC). The associations among Ki67, N-cadherin, and FBXO2 expression, as well as the clinicopathological parameters, were analyzed. Survival curves were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were performed to explore the prognostic significance of Ki67, N-cadherin, and FBXO2 expression. We found that the positive rates of Ki67, N-cadherin and FBXO2 expression in CRC tissue samples were 55.9%, 65.1%, 62.6%, respectively. The high expression levels of Ki67 and N-cadherin were significantly correlated with CRC size (P = 0.01) and metastasis (P = 0.01), respectively. The high expression level of FBXO2 was significantly correlated with CRC metastasis (P = 0.04) and AJCC stage (P = 0.029). A Cox regression analysis revealed that FBXO2 is an independent prognostic factor for CRC patients (HR 1.817, 95% CI 1.106-2.983, P = 0.018). FBXO2 may serve as a biomarker for metastasis and a reliable predictor for poor prognosis in CRC patients.

miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer.

Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo. HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.

Multi-institutional prospective study of nedaplatin plus S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens.

BACKGROUND: In this multi-institutional prospective study, we aimed to assess the safety and efficacy of nedaplatin plus S-1 (NS) chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) when platinum-containing regimens failed. METHODS: A total of 52 recurrent and metastatic NPC patients who previously received, but failed with platinum-containing chemotherapy, had oral S-1 chemotherapy (twice daily from the first day to the fourteenth day) and nedaplatin (80 mg/ m2, day 1) every 3 weeks. The body surface area (BSA) decided the dose of S-1: 40 mg twice a day when BSA < 1.25 m2; 50 mg twice daily when 1.25 m2 ⩽ BSA < 1.5 m2; and 60 mg twice daily when BSA ⩾ 1.5 m2. RESULTS: Treatment was well tolerated. The main hematological adverse event was neutropenia. Five patients (9.6%) had grade 3 neutropenia. Three patients were found with grade 3 anemia (5.8%). One patient was found with grade 3 thrombocytopenia (1.9%). No patient was found with grade 3 or 4 nonhematological toxicity. The rates of complete response, partial response and overall response were 3.8%, 38.5% and 42.3%, respectively. Median time to progression was 6.2 months and median survival was 14.6 months. The rates of 1-year survival and 2-year survival were 63% and 27%, respectively. CONCLUSIONS: NS chemotherapy provides a satisfactory and safe clinical activity for patients with recurrent and metastatic NPC after platinum-containing chemotherapy failed.

Phase II trial of docetaxel combined with nedaplatin for patients with recurrent and metastatic nasopharyngeal carcinoma.

PURPOSE: This Phase II trial was designed to evaluate the efficacy and safety of docetaxel combined with nedaplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. METHODS: In this multicenter Phase II trial, the patients were treated with intravenous docetaxel (75 mg/m(2), day 1) and nedaplatin (80 mg/m(2), day 1), each cycle repeated every 3 weeks for two cycles at least. RESULTS: From January 2010 to November 2013, a total of 78 patients were recruited in this trial. Among them, 73 patients were assessable for response. The treatment was well tolerated. The main hematological adverse event was neutropenia. A total of 12 patients (15.4%) had grade 3 or grade 4 neutropenia. Grade 3 anemia was observed in six patients (7.7%) and no grade 3/4 thrombocytopenia was observed. No Grade 3/4 non-hematological toxicity was observed. There were five complete response (6.8%), 43 partial responses (58.9%), and the overall response rate was 65.8% (95% confidence interval [CI], 48.7%-81.2%). With a median follow-up period of 18.6 months, the median time to progression was 7.9 months (95% CI, 4.2-10.8 months), median overall survival was 15.7 months (95% CI, 11.6-18.5 months). CONCLUSION: Docetaxel combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile as first-line chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma.

Both splenic CD5(+) B and CD5(-) B cells produce platelet glycoprotein-specific autoantibodies in chronic ITP.

The objective of the present study is to determine splenic B-cell subsets and the ability of splenic CD5(+) B and CD5(-) B cells to produce platelet glycoprotein-specific autoantibodies in chronic idiopathic thrombocytopenic purpura (ITP). Splenic CD5(+) B cells were identified by two-color flow cytometric analysis in eight ITP patients. Magnetic activated cell sorting (MACS) purified splenic CD5(+) B cells and CD5(-) B cells were cultured separately in vitro. Glycoprotein-specific autoantibodies in culture supernatants and plasma were measured by modified monoclonal antibody immobilization of platelet antigen (MAIPA) assay. The percentage of splenic CD5(+) B cells in ITP patients was slightly higher than that in controls, with no statistical significance. Four ITP patients displayed plasma IgG autoantibodies against both GPIIb/IIIa and GPIb. Moreover, splenic CD5(+) B cells and CD5(-) B cells from these four ITP patients also produced high level of IgG anti-GPII(b)/III(a) and anti-GPI(b) antibodies. However, we were unable to detect IgM GP-specific autoantibodies in culture supernatant and plasma in these ITP patients. It is concluded that both splenic CD5(+) B cells and CD5(-) B cells produce platelet IgG GP-specific autoantibodies, and may all play a role in the pathogenic process of ITP.

Changes in the level of serum liver enzymes after laparoscopic surgery.

AIM: The purpose of this study was to investigate the effect of laparoscopic surgery on liver function in humans and the possible mechanisms behind such effect. METHODS: Blood samples from 286 patients who underwent laparoscopic cholecystectomy (LC) and 40 patients who underwent open cholecystectomy (OC) were tested for liver function by measuring the level of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) before and after the operations. The same tests were also applied to 18 laparoscopic colorectal cancer resection (LCR) patients and 23 open colorectal cancer resection (OCR) patients to determine whether CO(2) pneumoperitoneum could alter the serum liver enzymes. RESULTS: The level of serum ALT and AST increased significantly during the first 48 hours post operations in both LC and LCR patients. However, no significant change of the serum liver enzymes was detected in both OC and OCR patients. As a result, there was statistically significant difference in change of both ALT and AST levels between LC and OC patients and LCR and OCR patients, respectively. By the 7(th) day post operation, the level of both enzymes returned to normal values in LC, OC and OCR patients except LCR patients whose enzymes remained at a higher level. CONCLUSION: Transient elevation of hepatic transaminases occurred after laparoscopic surgery. The major causative factor seemed to be the CO(2) pneumoperitoneum. In most of the laparoscopic surgery patients, the transient elevation of serum liver enzymes showed no apparent clinical implications. However, if preoperative liver function was very poor, laparoscopic surgery may not be the best choice for the treatment of patients with certain abdominal diseases.