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Surgical site infection (SSI) in thoracic surgery remains a significant cause of morbidity and prolonged hospitalization. Minimally invasive surgery (MIS) has significantly reduced the risk of SSI. We intended to compare whether there was difference between video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS) in SSI and highlight possible factors influencing SSI in lobectomy.This retrospective study analyzed patients who underwent minimally invasive lobectomy from January 2018 to December 2019. All patients' clinical characteristics and surgery-related information which may be related to the likelihood of SSI were recorded.A total of 1231 patients' records were reviewed with 806 VATS and 425 RATS. SSI was classified as deep or superficial SSI. Eighty-six (7.0%) patients were found to develop an SSI with 62 patients having deep infections and 24 had superficial infection. No statistical difference in the incidence rate and category of SSI was observed between patients undergoing VATS and RATS.There was no difference in the incidence of SSI between VATS and RATS lobectomy. Male gender, heavy smoking, uncontrolled diabetes mellitus, body mass index (BMI) 27.9, more blood loss, and the higher National Healthcare Safety Network (NHSN) risk index score (1 or 2) were the independent risk factors of SSI following minimally invasive lobectomy, while male gender, uncontrolled diabetes mellitus, BMI 27.9, more blood loss and the higher NHSN risk index score (1 or 2) were the main predictors of deep SSI.

We sought to analyze the prognostic significance of lung adenocarcinoma classification for patients with pathological N0 (pN0) lung invasive adenocarcinomas ≤1 cm who underwent surgical resection and investigate the optimal surgical procedure according to lung adenocarcinoma classification.A total of 1409 consecutive patients with resected pN0 invasive lung adenocarcinoma ≤1 cm were retrospectively reviewed. Comprehensive histologic subtyping was determined according to IASLC/ATS/ERS lung adenocarcinoma classification. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients receiving lobectomy, segmentectomy, and wedge resection.RFS and OS favored lobectomy and segmentectomy compared with wedge resection in the entire cohort. Five-year RFS rates were 100%, 98.2%, 97.3%, 77.8%, and 82.8% (p 0.001) for lepidic, acinar, papillary, micropapillary, and solid predominant subtypes, while 5-year OS rates were 100%, 98.4%, 98.1%, 88.9%, and 96.5% (p 0.001), respectively. Multivariate analysis showed that adenocarcinoma predominant pathological subtype and CT appearance were independent prognostic factors for RFS, and surgical procedure was independent factor for both RFS and OS. Specifically, wedge resection showed worse survival compared with anatomical resection in patients with papillary, micropapillary, or solid predominant subtypes, whereas in patients with lepidic predominant and acinar predominant subtypes, wedge resection showed comparable RFS with anatomical resection.Anatomical resection showed better survival for patients with pN0 invasive lung adenocarcinoma ≤1 cm. For patients with invasive adenocarcinoma ≤1 cm in whom anatomical resection is not feasible, wedge resection could provide similar oncological effect when tumor is lepidic predominant or acinar predominant.

Rationale: Resistance to pemetrexed (PEM)-based chemotherapy is a major cause of progression in non-small cell lung cancer (NSCLC) patients. The deubiquitinating enzyme UCHL1 was recently found to play important roles in chemoresistance and tumor progression. However, the potential roles and mechanisms of UCHL1 in PEM resistance remain unclear. Methods: Bioinformatics analyses and immunohistochemistry were used to evaluate UCHL1 expression in NSCLC specimens. Kaplan-Meier analysis with the log-rank test was used for survival analyses. We established PEM-resistant NSCLC cell lines by exposing them to step-wise increases in PEM concentrations, and in vitro and in vivo assays were used to explore the roles and mechanisms of UCHL1 in PEM resistance using the NSCLC cells. Results: In chemoresistant tumors from NSCLC patients, UCHL1 was highly expressed and elevated UCHL1 expression was strongly associated with poor outcomes. Furthermore, UCHL1 expression was significantly upregulated in PEM-resistant NSCLC cells, while genetic silencing or inhibiting UCHL1 suppressed resistance to PEM and other drugs in NSCLC cells. Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. Furthermore, UCHL1 upregulated TS expression, which mitigated PEM-induced DNA damage and cell cycle arrest in NSCLC cells, and also conferred resistance to PEM and other drugs. Conclusions: It appears that UCHL1 promotes PEM resistance by upregulating TS in NSCLC cells, which mitigated DNA damage and cell cycle arrest. Thus, UCHL1 may be a therapeutic target for overcoming PEM resistance in NSCLC patients.

Background Chemoresistance is the major cause of neoadjuvant treatment failure in breast cancer patients. Despite recent progress, the mechanism underlying chemoresistance remains to be further defined. Methods Expression of G protein-coupled receptor 120 (GPR120) was analyzed by immunohistochemistry in the biopsies of primary breast cancer who subsequently underwent preoperative neoadjuvant chemotherapy. In vitro and in vivo loss- and gain-of -function studies were performed to reveal the effects and related mechanism of GPR120 signaling pathway in the chemoresistance of breast cancer cells. Findings We identified that GPR120, a receptor for long-chain fatty acids, was important for the acquisition of chemoresistance in breast cancer cells. We showed that GPR120 expression was positively associated with clinical response to neoadjuvant chemotherapy in patients. In breast cancer cells, GPR120 enhanced the de novo synthesis of fatty acids that served as GPR120 ligands to activate GPR120 signaling via a feedback mechanism. Upregulated GPR120 signaling rendered cells resistant to epirubicin-induced cell death by upregulating ABC transporters expression and thus decreasing the intracellular accumulation of epirubicin. Akt/NF-κB pathway was responsible for the GPR120-mediated expression of ABC transporters leading to modulation of the concentration of chemotherapeutic drugs in cells. The functional importance of GPR120 in chemoresistance was further validated using epirubicin-treated tumor xenografts, in which we showed that blockade of GPR120 signaling with AH7614 or GPR120-siRNA significantly compromised chemoresistance. Interpretation Our results highlight that GPR120 might be a promising therapeutic target for breast cancer chemoresistance. Fund National Natural Science Foundation of China, Ministry of Science and Technology of China, Program of Science and Technology Commission of Shanghai Municipality.

Metastasis is a major cause of breast cancer-associated mortality. Natural products extracted from herbs provide rich bioactive compounds with anticancer efficacy but may have limited or moderate potency and considerable toxicity. We developed a novel aziridonin, YD0514, by aziridinating oridonin, a natural product of the medicinal herb Rabdosia rubescens. In this study, we found that YD0514 significantly inhibited proliferation, motility, and adhesion of metastatic breast cancer cell lines MDA-MB-231, GI101, GILM2, and GILM3. YD0514 also decreased the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9), focal adhesion kinase (FAK), and integrin family members. Importantly, YD0514 suppressed the growth of metastatic breast cancer xenograft tumors and significantly inhibited lung metastasis in vivo. Lastly, we showed that YD0514's anti-metastatic effect on highly aggressive breast cancer is mediated via regulating the NRF-2/RHOA/ROCK signaling pathway. These results demonstrate that YD0514, the first active analog based on an oridonin D-ring modification, has the potential to be developed as an anti-metastasis therapy for patients with metastatic cancers.

Background Evidence suggests that fatty acid receptor FFAR4 plays a tumor-promoting role in adipose tissue-adjacent malignancies, but its clinical relevance remains unexplored. Here, we investigated the clinical significance and underlying mechanisms of FFAR4 in hormone receptor-positive breast cancer (HRPBC). Methods FFAR4 expression was assessed by immunohistochemistry in an exploration cohort of 307 breast cancer cases collected from two independent institutes. Two public breast cancer microarray datasets served as validation cohorts. Gas chromatography-mass spectrometry was employed to identify FFAR4 ligands in normal and cancerous breast tissues. Survival analyses were performed in all cohorts and designated molecular subgroups. Mechanistic studies were performed in vitro in hormone receptor-positive breast cancer cell lines MCF-7 and T-47D. Results Aberrant FFAR4 expression and endogenous FFAR4 ligands were identified in breast cancer tissues, five FFAR4 ligands showed significantly elevated proportions in cancerous versus normal tissues. In the exploration cohort, FFAR4 was demonstrated as an independent prognostic factor for recurrences (HR: 2.183, 95% CI: 1.360–3.504, P = 0.001) and breast cancer-specific deaths (HR: 2.102, 95% CI: 1.173–3.766, P = 0.013) in HRPBC cases. In contrast, FFAR4 expression was not associated with prognosis in hormone receptor-negative cases. In the validation cohorts, FFAR4 mRNA levels were also observed to be associated with disease recurrence in estrogen receptor-positive cases, but not so in estrogen receptor-negative cases. FFAR4 activation by endogenous ligands and a synthetic ligand TUG891 significantly dampened tamoxifen’s efficacy on HRPBC cells, whereas FFAR4 knockdown or antagonist AH7614 abrogated this effect. Furthermore, FFAR4-induced tamoxifen resistance was dependent on ERK and AKT pathways in HRPBC. Conclusions Our results establish a novel role of FFAR4 and its ligands in the complicated interactions between tissue lipid profile and cancer biology. FFAR4 signaling confers tamoxifen resistance in HRPBC cell line and FFAR4 expression can serve as a prognostic biomarker for tamoxifen-treated HRPBC patients. FFAR4 may serve as a potential target for anti-breast cancer therapies, especially in endocrine resistant cases. Electronic supplementary material The online version of this article (10.1186/s13046-019-1040-3) contains supplementary material, which is available to authorized users.

Introduction Gastric cancer (GC) is one of the most frequent malignant tumours worldwide and is associated with high invasiveness, high metastasis and poor prognosis. Cancer-associated fibroblasts (CAFs), residing around tumour cells in tumour stroma, are important modifiers of tumour initiation and progression. However, the molecular mechanisms by which CAF’s modulate tumour development have yet not to be characterised in GC. Material and methods CAFs and normal fibroblasts (NFs) were cultured from resected gastric cancer tissues and patient matching non-cancerous tissues. The expression of Lumican in gastric CAFs was detected by quantitative RT-PCR and Westerblot. The effects of CAFs, which was interfered with Lumican, on gastric cancer cell proliferation, migration and invasion in vitro were measured. were measured by CCK8, the coculture migration or matrigel invasion assay, respectively. In vivo tumorigenesis and metastasis were performed by injection CAFs and GC cells subcutaneously or peritoneally. Results and discussions Lumican, an extracellular matrix protein, is highly expressed in human gastric CAFs and its expression is positively associated with depth of invasion, lymph node metastasis, TNM stage and poor survival rate of GC. Knockdown of Lumican in CAFs impaired the GC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and peritoneal metastasis in vivo. Further functional studies revealed that integrin beta1-FAK signalling pathway mediated the promoting effects of stromal Lumican on GC cell metastasis potential. Conclusion CAF-derived Lumican contributes to tumorigenesis and metastasis of GC by activating the integrin b1-FAK signalling pathway.Targeting stromal Lumican may provide a potential treatment strategy for GC.

Humanized mouse models have been developed and utilized in cancer research for decades. Newly developed combined immunodeficient NOD-SCID-IL2rg–/– mice are more permissive for human cells and tissue engraftment. In this review, we discuss the use of NOD-SCID-IL2rg(–/–) mice as a preclinical tool in cancer research and its potential use for individualized cancer therapies.

The expression of Aurora B in normal endometria and endometrial carcinomas and its relation with clinicopathologic parameters of endometrial carcinomas were investigated. Streptavidin-biotin peroxidase (SP) immunohistochemical technique was used to detect the expression of Aurora B in 10 cases of normal proliferative phase endometria, 10 cases of normal secretory phase endometria and 72 cases of endometrial carcinomas respectively. According to the 1988 International Federation of Gynecology and Obstetrics (FIGO) grade, there were 37 patients in grade 1, 23 in grade 2 and 12 in grade 3 respectively. According to the FIGO stage, there were 59 patients in stage I-II and 13 patients in stage III-IV. Aurora B was expressed in both normal proliferative phase endometria, secretory phase endometria and endometrial carcinomas, but its positive labeling index (PLI) in proliferative phase endometria was significantly higher than that in secretory phase endometria (P0.01) and endometrial carcinomas (P0.01). The PLI of Aurora B was lower in tumors with well differentiation (G(1)), low surgical staging (I-II), andor=1/2 myometrial invasion than that in tumors with moderate and low differentiation (G(2)-G(3)), higher surgical staging (III-IV), and1/2 myometrial invasion (all P0.01). Aurora B exerts its functions in the replication of normal endometrial glandular cells; Expression of Aurora B is significantly correlated with biologic behavior of endometrial carcinoma, indicating that Aurora B may be a promising prognostic factor in endometrial carcinoma.