Surgical Resection of Primary Tumors Provides Survival Benefits for Lung Cancer Patients With Unexpected Pleural Dissemination

Background: Surgery is not generally recommended for non-small cell lung cancer (NSCLC) patients with malignant pleural dissemination (PD). However, in some cases, PD is found unexpectedly during surgery. There is no consensus on whether surgical intervention can provide survival benefit for them. We investigated the role of surgery in NSCLC patients with unexpected PD by a cohort study.Methods: Clinical data of consecutive patients who intended to undergo radical surgery for NSCLC between January 2010 and December 2015 at Shanghai Chest Hospital and Huadong Hospital were collected from a lung cancer database. Patients diagnosed with unexpected malignant pleural nodules intraoperatively were enrolled in this retrospective study.Results: A total of 181 NSCLC patients were diagnosed with unexpected malignant PD intraoperatively and confirmed with postoperatively histological examinations. Out of these, 80 (44.2%) patients received pleural nodule biopsies alone, and 101 (55.8%) received primary tumor resection (47 with sublobar resection and 54 with lobectomy). The median progression-free survival and overall survival for all patients were 13 and 41 months respectively. Patients in the resection group had significantly better progression-free survival (19.0 vs. 10.0 months, P < 0.0001) and overall survival (48.0 vs. 33.0 months, P < 0.0001) than patients in the biopsy group. In the resection group, there was no statistical difference between patients with sublobar resection and lobectomy (P = 0.34). Univariate and multivariate analyses identified primary tumor resection, targeted adjuvant therapy, and tumor size (≤ 3 cm) as independent prognostic factors.Conclusions: NSCLC patients with unexpected intraoperative PD potentially benefited from surgical resection of the primary tumor and multidisciplinary targeted therapy, particularly when tumor size did not exceed 3 cm. Our data demonstrated that the resection type was not associated with survival differences, which remains to be defined with a larger sample size

pN1 but not pN0/N2 predicts survival benefits of prophylactic cranial irradiation in small-cell lung cancer patients after surgery.

Background Prophylactic cranial irradiation has been shown to reduce brain metastases and provide survival benefits in small-cell lung cancer (SCLC). However, its role in limited-stage SCLC patients after surgery remains unclear. Further, it is unknown whether the effect of prophylactic cranial irradiation is generalizable in these patients with different pathological nodal (N0-N2) stages, a state indicating the presence of tumor metastases. Methods We combined data from a single medical center and Surveillance, Epidemiology, and End Results database. Propensity score matching analyses were performed (1:2) to evaluate the role of prophylactic cranial irradiation in SCLC patients after surgery. Cox proportional hazards regression model was used to identify predictors of survival. Results 124 (18.7%) out of 664 surgically-treated SCLC patients received prophylactic cranial irradiation treatment. Within the entire cohort, multivariate Cox regression analysis identified dataset source, age, pathological T and N stages, adjuvant chemotherapy, resection type, and histology as independent prognostic factors for overall survival. Prophylactic cranial irradiation appeared to be associated with a better overall survival, but the difference is marginally significant (P=0.063). Further, we stratified patients based on the pathological N0-N2 stages using propensity score matching analyses, which showed that prophylactic cranial irradiation treatment was superior to non-prophylactic cranial irradiation treatment for surgically-treated SCLC patients with N1 stage only (univariate analysis: P=0.026; multivariate Cox: P=0.004), but not N0/N2 stage (univariate analysis: P=0.65 and P=0.28, respectively; multivariate Cox: P=0.99 and P=0.35, respectively). Conclusions Prophylactic cranial irradiation provides survival benefits for SCLC patients with pN1 after surgery but not with pathological N0/N2 stage. Our findings may provide helpful stratifications for clinical decision-making of prophylactic cranial irradiation intervention in SCLC patients

Self-Lubricating Polytetrafluoroethylene/Polyimide Blends Reinforced with Zinc Oxide Nanoparticles

ZnO nanoparticle reinforced polytetrafluoroethylene/polyimide (PTFE/PI) nanocomposites were prepared and their corresponding tribological and mechanical properties were studied in this work. The influences of ZnO loading, sliding load, and velocity on the tribological properties of ZnO/PTFE/PI nanocomposites were systematically investigated. Results reveal that nanocomposites reinforced with 3 wt% ZnO exhibit the optimal tribological and mechanical properties. Specifically, the wear loss decreased by 20% after incorporating 3 wt% ZnO compared to unfilled PTFE/PI. Meanwhile, the impact strength, tensile strength, and elongation-at-break of 3 wt% ZnO/PTFE/PI nanocomposite are enhanced by 85, 5, and 10% compared to pure PTFE/PI blend. Microstructure investigation reveals that ZnO nanoparticles facilitate the formation of continuous, uniform, and smooth transfer film and thus reduce the adhesive wear of PTFE/PI

Golgi Apparatus-Localized Synaptotagmin 2 Is Required for Unconventional Secretion in Arabidopsis

BACKGROUND: Most secretory proteins contain signal peptides that direct their sorting to the ER and secreted via the conventional ER/Golgi transport pathway, while some signal-peptide-lacking proteins have been shown to export through ER/Golgi independent secretory pathways. Hygromycin B is an aminoglycoside antibiotic produced by Streptomyces hygroscopicus that is active against both prokaryotic and eukaryotic cells. The hygromycin phosphotransferase (HYG(R)) can phosphorylate and inactivate the hygromycin B, and has been widely used as a positive selective marker in the construction of transgenic plants. However, the localization and trafficking of HYG(R) in plant cells remain unknown. Synaptotagmins (SYTs) are involved in controlling vesicle endocytosis and exocytosis as calcium sensors in animal cells, while their functions in plant cells are largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found Arabidopsis synaptotagmin SYT2 was localized on the Golgi apparatus by immunofluorescence and immunogold labeling. Surprisingly, co-expression of SYT2 and HYG(R) caused hypersensitivity of the transgenic Arabidopsis plants to hygromycin B. HYG(R), which lacks a signal sequence, was present in the cytoplasm as well as in the extracellular space in HYG(R)-GFP transgenic Arabidopsis plants and its secretion is not sensitive to brefeldin A treatment, suggesting it is not secreted via the conventional secretory pathway. Furthermore, we found that HYG(R)-GFP was truncated at carboxyl terminus of HYG(R) shortly after its synthesis, and the cells deficient SYT2 failed to efficiently truncate HYG(R)-GFP,resulting in HYG(R)-GFP accumulated in prevacuoles/vacuoles, indicating that SYT2 was involved in HYG(R)-GFP trafficking and secretion. CONCLUSION/SIGNIFICANCE: These findings reveal for the first time that SYT2 is localized on the Golgi apparatus and regulates HYG(R)-GFP secretion via the unconventional protein transport from the cytosol to the extracelluar matrix in plant cells

NHX antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development

AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the ER-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were co-localized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+-leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes

Multi-scale integrative analyses identify THBS2+ cancer-associated fibroblasts as a key orchestrator promoting aggressiveness in early-stage lung adenocarcinoma.

Rationale: Subsets of patients with early-stage lung adenocarcinoma (LUAD) have a poor post-surgical course after curative surgery. However, biomarkers stratifying this high-risk subset and molecular underpinnings underlying the aggressive phenotype remain unclear. Methods: We integrated bulk and single-cell transcriptomics, proteomics, secretome and spatial profiling of clinical early-stage LUAD samples to identify molecular underpinnings that promote the aggressive phenotype. Results: We identified and validated THBS2, at multi-omic levels, as a tumor size-independent biomarker that robustly predicted post-surgical survival in multiple independent clinical cohorts of early-stage LUAD. Furthermore, scRNA-seq data revealed that THBS2 is exclusively derived from a specific cancer-associated fibroblast (CAF) subset that is distinct from CAFs defined by classical markers. Interestingly, our data demonstrated that THBS2 was preferentially secreted via exosomes in early-stage LUAD tumors with high aggressiveness, and its levels in the peripheral plasma associated with short recurrence-free survival. Further characterization showed that THBS2-high early-stage LUAD was characterized by suppressed antitumor immunity. Specifically, beyond tumor cells, THBS2+ CAFs mainly interact with B and CD8+ T lymphocytes as well as macrophages within tumor microenvironment of early-stage LUAD, and THBS2-high LUAD was associated with decreased immune cell infiltrates but increased immune exhaustion marker. Clinically, high THBS2 expression predicted poor response to immunotherapies and short post-treatment survival of patients. Finally, THBS2 recombinant protein suppressed ex vivo T cells proliferation and promoted in vivo LUAD tumor growth and distant micro-metastasis. Conclusions: Our multi-level analyses uncovered tumor-specific THBS2+ CAFs as a key orchestrator promoting aggressiveness in early-stage LUAD