The ability of natural killer (NK) cells to mediate potent antitumor immunity in clinical adoptive transfer settings relies, in large part, on their ability to retain cytotoxic function following cryopreservation. To avoid potential systemic toxicities associated with infusions of NK cells into patients in the presence of dimethylsulfoxide (DMSO), interest in alternative cryoprotective agents (CPAs) with improved safety profiles has grown. Despite the development of various sugars, amino acids, polyols, and polyampholytes as cryoprotectants, their ability to promote protection from intracellular cryodamage is limited because they mostly act outside of the cell. Though ways to shuttle cryoprotectants intracellularly exist, NK cells' high aversity to manipulation and freezing has meant they are highly understudied as targets for the development of new cryopreservation approaches. Here, the first example of a safe and efficient platform for the intracellular delivery of non‐DMSO CPAs to NK cells is presented. Biocompatible chitosan‐based nanoparticles are engineered to mediate the efficient DMSO‐free cryopreservation of NK cells. NK cells cryopreserved in this way retain potent cytotoxic, degranulation, and cytokine production functions against tumor targets. This not only represents the first example of delivering nanoparticles to NK cells, but illustrates the clinical potential in manufacturing safer allogeneic adoptive immunotherapies “off the shelf.”
Background: The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle. Methods: RT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes. Results: LBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression. Conclusion: In a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.
Introduction: Laparoscopy-assisted radical total gastrectomy is technically demanding. Aim: To introduce the "enjoyable space" approach to achieve D2 plus complete mesogastrium excision (CME) and to investigate its safety and feasibility. Material and methods: Between January 2015 and December 2017, 165 patients with primary advanced upper gastric cancer underwent laparoscopy-assisted radical total gastrectomy. Among these patients, 81 underwent conventional D2 total gastrectomy (D2 group) and 84 underwent D2 plus CME total gastrectomy (D2 + CME group). Clinicopathological characteristics, surgical outcomes and postoperative complications were compared between the two groups. Results: There were no significant differences between the two groups (p > 0.05) in clinicopathological characteristics. However, the D2 + CME group had a longer mean operative time, lower mean blood loss and slightly higher mean number of retrieved lymph nodes (LNs) than the D2 group (p < 0.05 each). The mean time to first flatus, liquid diet, and soft diet and the duration of hospital stay were similar between the two groups (p > 0.05 each). No significant difference in postoperative complication rates was found between the groups (16.0% vs. 9.5%, p > 0.05). Conclusions: The "enjoyable space" approach is an option to achieve D2 + CME, and its safety and feasibility over conventional method are confirmed with lower intraoperative blood loss and more harvested LNs.
Ovarian cancer is known for its aggressive pathological features, including the capacity to undergo epithelial to mesenchymal transition, promoting angiogenesis, metastatic potential, chemoresistance, inhibiting apoptosis, immunosuppression and promoting stem-like features. Galectins, a family of glycan-binding proteins defined by a conserved carbohydrate recognition domain, can modulate many of these processes, enabling them to contribute to the pathology of ovarian cancer. Our goal herein was to review specific galectin members identified in the context of ovarian cancer, with emphasis on their association with clinical and pathological features, implied functions, diagnostic or prognostic potential and strategies being developed to disrupt their negative actions.
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