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This multicenter, randomized, double-blind, parallel-controlled trial aimed to compare the pharmacokinetics (PK) of IBI301 with rituximab in patients with CD20-positive (CD20+) B-cell lymphoma, who achieved a complete response/unconfirmed complete response after standard treatments. Patients were randomized (1:1) to receive IBI301 or rituximab (375 mg/m2, IV). Patients who continuously benefitted from the trial after the PK phase underwent the extension phase to receive up to three cycles of 3-month-cycle of rituximab/IBI301 maintenance therapy. PK was described using the area under the serum concentration–time curve from time zero to infinity (AUC0-inf), AUC from time zero to last quantifiable concentration (AUC0-t), and maximum serum concentration (Cmax). Pharmacodynamics (PD), incidence of adverse events and immunogenicity were evaluated. PK was defined equivalent, if 90% confidence intervals (CIs) for geometric mean ratios of PK endpoints fell within the margin of 0.8–1.25. Overall, 181 patients were enrolled in IBI301 (n = 89) and rituximab (n = 92) groups. Geometric mean ratios of AUC0-inf, AUC0-t, and Cmax were 0.91 (90% CI 0.85, 0.97), 0.91 (90% CI 0.86, 0.97), and 0.96 (90% CI 0.92, 1.01) between treatment groups, all within the bioequivalence range. Peripheral CD19+ and CD20+ B-cell counts were similar at each prespecified time point between the groups. No difference in immunogenicity was observed. The incidences of treatment-emergent adverse events (84.3% vs. 83.5%) and treatment-related AEs (56.2% vs. 61.5%) were comparable (IBI301 vs. rituximab). IBI301 was PK bioequivalent to rituximab in patients with CD20+ B-cell lymphoma. The PD, safety, and immunogenicity profiles of IBI301 were similar to those of rituximab.

There are limited therapeutic methods for triple negative breast cancer in the clinic, which is easy to progress into the brain to form metastatic lesions and evolve into the terminal stage. Because both the primary cancer and the brain metastasis have high glycolysis, we hypothesize that lactate dehydrogenase (LDH), which catalyzes the final step of glycolysis, may be a predictor, as well as a treatment target, for breast cancer brain metastasis. Therefore, the expression of LDH-A was detected on 119 triple negative breast cancer tissues with immunohistochemistry, and the serum LDH levels were also measured. Our results showed that the LDH-A expression inside the tumor was significantly higher than the matched normal tissues. Tumor LDH-A expression, serum LDH status, and the slope of serum LDH status were closely associated with triple negative breast cancer brain metastasis and brain metastasis free survival. This study indicates that tumor LDH and serum LDH status are two predictors for triple negative breast cancer brain metastasis.

Scientific Reports 7: Article number: 42069; published online: 03 February 2017; updated: 11 April 2017 The original version of this Article contained an error in the order of the authors, where “Xinmei Kang, Ximing Guo, Xingjian Niu, Weiwei An, Suhan Li, Zhaoliang Liu, Yue Yang, Na Wang, Qicheng Jiang, Caichuan Yan, Hui Wang and Qingyuan Zhang” was incorrectly given as “Xinmei Kang, Ximing Guo, Weiwei An, Xingjian Niu, Suhan Li, Zhaoliang Liu, Yue Yang, Na Wang, Qicheng Jiang, Caichuan Yan, Hui Wang and Qingyuan Zhang”.

Gold nanorods are effective photothermal agents in diagnosis and treatment of cancer due to their specific near-infrared laser absorption. However, tumor photothermal therapy by nanorods alone is lack of targeting. Here, we described a novel nanocomplex made up of gold nanorods, porphyrin, and trastuzumab, called TGNs and investigated the TGN-mediated photothermal therapy as a potential alternative treatment of targeting HER2-positive breast cancers. By conjugating trastuzumab and porphyrin to the surface of gold nanorods, we have increased the targeting specificity and amplified the detecting effectiveness at the same time. TGN-mediated photothermal ablation by near-infrared laser led to a selective destruction of HER2-positive cancer cells and significantly inhibited tumor growth in mouse models bearing HER2 over-expressed breast cancer xenograft with less toxicity. Moreover, TGNs provided better therapeutic efficacy in comparison with the conventional molecule targeted therapy. Our current data suggest a highly promising future of TGNs for its therapeutic application in trastuzumab-resistant breast cancers.

The prognostic value of programmed death-ligand 1 (PD-L1) in gastric cancer (GC) remains controversial. To clarify this problem, we performed a meta-analysis of research studies identified in the PubMed, EMBASE and the Cochrane Library databases. A total of 1,901 patients in 10 studies were enrolled in this meta-analysis, and the pooled hazard ratio (HR) of 1.64 (95% CI 1.11 to 2.43; P = 0.01) indicated that PD-L1 expression is associated with a shorter overall survival (OS). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with tumour size (OR = 1.87, 95% CI 1.25 to 2.78; P = 0.002) and lymph node status (OR = 2.17, 95% CI 1.04 to 4.52; P = 0.04). However, PD-L1 had no correlation with gender, age, cancer location, differentiation, depth of invasion, and tumour stage. This meta-analysis indicates that PD-L1 expression is a valuable predictor of the prognosis of patients with GC. PD-L1 expression could be used for identifying a subgroup of patients, who would potentially benefit from targeted therapy against PD-1 or PD-L1. Well-designed large-cohort studies are needed to confirm these findings.

Chemoresistance is a poor prognostic factor in breast cancer and is a major obstacle to the successful treatment of patients receiving chemotherapy. However, the precise mechanism of resistance remains unclear. In this study, a pair of breast cancer cell lines, MCF-7 and its adriamycin-resistant counterpart MCF-7/ADR was used to examine resistance-dependent cellular responses and to identify potential therapeutic targets. We applied nanoflow liquid chromatography (nLC) and tandem mass tags (TmT) quantitative mass spectrometry to distinguish the differentially expressed proteins (DEPs) between the two cell lines. Bioinformatics analyses were used to identify functionally active proteins and networks. 80 DEPs were identified with either up- or down-regulation. Basing on the human protein-protein interactions (PPI), we have retrieved the associated functional interaction networks for the DEPs and analyzed the biological functions. Six different signaling pathways and most of the DEPs strongly linked to chemoresistance, invasion, metastasis development, proliferation and apoptosis. The identified proteins in biological networks served to resistant drug and to select critical candidates for validation analyses by western blot. The glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl cyclotransferase (GGCT), isocitrate dehydrogenase 1 (NADP+,soluble)(IDH1), isocitrate dehydrogenase 2 (NADP+,mitochondrial) (IDH2) and glutathione S-transferase pi 1(GSTP1), five of the critical components of GSH pathway, contribute to chemoresistance.