Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665–miR98–AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

Summary The long-term outcomes of robotic-assisted McKeown esophagectomy (RAME) compared to thoraco-laparoscopic McKeown esophagectomy (TLME) for the patients with esophageal squamous cell carcinoma (ESCC) remain unclear. The aim of this study was to compare the number of dissected lymph nodes and long-term survival between RAME and TLME using a propensity score-matched (PSM) analysis. A total of 721 patients undergoing minimally invasive McKeown esophagectomy at our department from February 2015 to October 2019 were analyzed, including 310 patients in RAME group and 411 in TLME group. The exact numbers of lymph nodes including those among thoracic and abdominal categories as well as those along the recurrent laryngeal nerve (RLN) were all recorded. PSM analysis was applied to generate matched pairs for further comparison. All patients with R0 resection were followed with a strict follow-up period which range from 1 to 56 months. The effect of lymphadenectomy was compared between all patients in unmatched and matched groups. Long-term outcomes consisting of overall survival (OS), disease-free survival (DFS) and recurrence rate (including regional recurrence rate, systemic recurrence rate and mediastinal lymph nodes recurrence rate) were compared in R0 resection patients. Finally, 292 patients were identified for each cohort after PSM. RAME was found to yield significantly more left RLN lymph nodes (mean: 2.27 ± 0.90 vs. 2.09 ± 0.79; P = 0.011) and more thoracic lymph nodes (mean: 12.60 ± 4.22 vs. 11.83 ± 3.12, P = 0.012) compared with TLME after PSM analysis. There was no significant difference in the OS and DFS between the RAME and TLME group. Besides, total recurrences were recognized in 33 (11.7%) patients in the RAME group and 36 (12.9%) in the TLME group (P = 0.676). The mediastinal lymph nodes recurrence rate in the RAME group was tended to be lower than that in the TLME group (2.5% vs. 5.4%, P = 0.079). Therefore, RAME might be an alternative approach for the treatment of ESCC with more lymph nodes dissected and similar long-term survival outcomes compared to TLME.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals, and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed “angiotrophism”. We found that polarizing macrophages towards a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes, and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has additive effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.

SUMMARY The aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (−2.03 ± 2.28 kg vs. −4.05 ± 3.13 kg, P = 0.012), BMI (−0.73 ± 0.79 kg/m2 vs. −1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (−1.10 ± 0.37 kg/m2 vs. −1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.