No abstract

Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines. Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di- O -isopropylidene- β -d-fructopyranose and 1,2:4,5-di- O -isopropylidene- β -d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis. Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells. Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

Background: To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. Methods: Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. Results: Twenty-two eligible clinical trials including 15676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89-0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89-0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99-1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19-13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40-3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95-5.06) and TN (pooled OR, 4.09; 95% CI, 2.71-6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83-2.04). Conclusions: The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

Purpose To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. a 10% increment of TILs in tumor and lymphocyte-predominant breast cancer (LPBC), on long-term survival and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes.Methods Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0.Results Twenty-two eligible clinical trials including 15676 unique patients were included for meta-analysis. The 10% increment of TILs in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89-0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89-0.92) breast tumors significantly improved overall survival (OS) but in Luminal tumor subtype was inert to improve that (pooled HR, 1.06; 95% CI, 0.99-1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19-13.5). LPBC was significantly related with a higher pCR rate (OR, 2.73; 95% CI, 2.40-3.01) than non-LPBC. This significant difference was also shown in different molecular subtypes of LPBC compared with those of non-LPBC. HER2-amplified (OR, 3.14; 95% CI, 1.95-5.06) and TN (OR, 4.09; 95% CI, 2.71-6.19) phenotypes of breast cancers expressed significantly elevated high-level TILs than Luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (OR, 1.30; 95%CI, 0.83-2.04).Conclusion The elevation of TILs in breast tumors predicts promising prognostic outcomes, particularly in the HER2-overexpression and TN subtypes. These benefits in Luminal tumor subtype need to be warranted.

Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines.Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di-O-isopropylidene-β-d-fructopyranose and 1,2:4,5-di-O-isopropylidene-β-d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis.Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells.Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.