CDK inhibitor Palbociclib targets STING to alleviate autoinflammation.

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.

Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis.

BACKGROUND: Micropapillary (MIP) component was a major concern in determining surgical strategy in lung adenocarcinoma (LUAD). We sought to develop a novel method for detecting MIP component during surgery. METHODS: Differentially expressed proteins between MIP-positive and MIP-negative LUAD were identified through proteomics analysis. The semi-dry dot-blot (SDB) method which visualises the targeted protein was developed to detect MIP component. RESULTS: Cellular retinoic acid-binding protein 2 (CRABP2) was significantly upregulated in MIP-positive LUAD (P < 0.001), and the high CRABP2 expression zone showed spatial consistency with MIP component. CRABP2 expression was also associated with decreased recurrence-free survival (P < 0.001). In the prospective cohort, the accuracy and sensitivity of detecting MIP component using SDB method by visualising CRABP2 were 82.2% and 72.7%, which were comparable to these of pathologist. Pathologist with the aid of SDB method would improve greatly in diagnostic accuracy (86.4%) and sensitivity (78.2%). In patients with minor MIP component (≤5%), the sensitivity of SDB method (63.6%) was significantly higher than pathologist (45.4%). CONCLUSIONS: Intraoperative examination of CRABP2 using SDB method to detect MIP component reached comparable performance to pathologist, and SDB method had notable superiority than pathologist in detecting minor MIP component.

Revisiting the Mg/TMSCl/Dipolar Solvent System for Dearomatic Silylation of Aryl Carbonyl Compounds: Substrate Scope, Transformations, and Mechanistic Studies.

Dearomatic silylation of arene derivatives is an intriguing synthetic target, which represents an elegant extension of Birch reduction and produces silylated cyclohexene derivatives with great potential of further transformation. Herein, we report a systematic study on dearomatic silylation of aryl carbonyl compounds with Mg and the TMSCl/NMP adduct. The protocol displays a wide range of substrate scope, including alkyl aryl ketones, aromatic amides, benzonitriles, tert-butyl benzoates, and even 2,2'-bipyridines. Synthetic utility is demonstrated using the products as versatile substrate in various transformations. The detailed mechanism is presented with both control experimental analyses and theoretical calculations. An unusual five-coordinated silicon dianion intermediate is first proposed and described here. The selectivity is influenced by the relative rates of single electron reductions (the TMSCl/NMP adduct versus the substrate) and the steric effects.

Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification to Upgrade Extracapsular Extension of Tumor in Nodes From R0 to Incomplete Resection.

INTRODUCTION: The International Association for the Study of Lung Cancer (IASLC) proposed a revised R classification to upstage extracapsular extension (ECE) of tumor in nodes from R0 to R1. Nevertheless, evidence to confirm this proposal is insufficient. METHODS: The study included 4061 surgical patients with NSCLC. After reclassification by IASLC-R classification, overall survival (OS) was analyzed to compare patients with ECE with those with R0, R(un), and incomplete resection (R1 and R2). The recurrence pattern of ECE was evaluated to determine whether it correlated with incomplete resection. RESULTS: Among 1136 patients with N disease, those without ECE (n = 754, 67%) had a significantly better OS than those with ECE (n = 382, 33%) (p < 0.001). This negative prognostic significance was consistent across multiple subgroups. Multivariate analysis revealed that ECE was an independent prognostic risk factor (p < 0.001). When patients with ECE were separated from the IASLC-R1 group, their OS was significantly worse than that of IASLC-R(un) patients, but comparable to that of the remaining patients in the IASLC-R1 patients when analyzing all patients and patients with N disease. Moreover, patients with ECE had an increased risk of local recurrence in the mediastinum (p < 0.001), ipsilateral lung (p = 0.031), and malignant pleural effusion or nodes (p = 0.004) but not distant recurrence including contralateral or both lungs (p = 0.268), liver (p = 0.728), brain (p = 0.252), or bone (p = 0.322). CONCLUSIONS: The prognosis of ECE patients is comparable with that of R1 patients. Moreover, their higher risk of local recurrence strongly suggests the presence of occult residual tumor cells in the surgical hemithoracic cavity. Therefore, upgrading ECE into incomplete resection is reasonable.

Protective effects of palbociclib on colitis-associated colorectal cancer.

Background: Chronic or recurrent inflammatory injury to the intestinal mucosa is closely related to inflammation-related colorectal cancer (CRC). This study aimed to examine the protective effects of palbociclib, a stimulator of interferon genes (STING) antagonist, on colitis-related colorectal carcinogenesis. Methods: Bioinformatic analyses, including Gene Ontology (GO) enrichment, gene set enrichment analysis (GSEA), and network analysis, were conducted. Male C57BL/6 mice were administered azoxymethane (AOM) and dextran sulfate sodium (DSS), followed by treatment with palbociclib for 6 weeks. The general conditions of mice were observed and recorded. The colon histopathology was assessed based on hematoxylin and eosin (H&E) staining results. Relative messenger RNA (mRNA) expression levels of interferon b1 (Ifnb1), interleukin 6 (Il6), and interleukin 1b (Il1b) in colon were estimated based on quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Results: The STING signaling pathway was significantly upregulated in stages III and IV of CRC in The Cancer Genome Atlas (TCGA)-CRC cohort. After treatment with AOM/DSS, the weight of mice decreased significantly, whereas administration of palbociclib partially reversed this trend. The mouse colon treated with AOM/DSS showed significant pathological damages, disorderly epithelial cell structure, atypical hyperplasia, and infiltration of several inflammatory cell types; however, the colon damage was remarkably reduced upon treatment with palbociclib. It was also found that palbociclib almost abolished the increase in the downstream effectors of STING-mediated transcription in the colon tissue treated with AOM/DSS, as evidenced by the transcription levels of Ifnb1, Il6, and Il1b. Conclusions: These findings indicate that the STING pathway is closely associated with CRC. Palbociclib significantly alleviates tumor development in AOM/DSS-induced colitis-associated CRC.

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity.

Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator. Brivanib markedly enhances cGAS-mediated type I IFN response in tumor cells treated with platinum. Mechanistically, brivanib directly targets cGAS and enhances its DNA binding affinity. Importantly, brivanib synergizes with cisplatin in tumor control by boosting CD8+ T cell response in a tumor-intrinsic cGAS-dependent manner, which is further validated by a patient-derived tumor-like cell clusters model. Taken together, our findings identify cGAS as an unprecedented target of brivanib and provide a rationale for the combination of brivanib with platinum-based chemotherapeutics in cancer treatment.

Is VATS approach suitable in re-operations for postoperative hemothorax after pulmonary resection? Data analysis in a big volume thoracic center.

OBJECTIVE: This study explored the safety and of feasibility of video-assisted thoracoscopy (VATS) in re-operations for post-operative hemothorax. METHODS: The clinical data of patients underwent re-operations due to post-operative hemothorax after pulmonary resection in Shanghai Pulmonary Hospital from 2006 to 2018 were retrospectively analysed. The incidence of re-operations were analyzed. The mortality and morbidity were compared between thoracotomy and thoracoscopic procedure for re-exploration. RESULTS: A total of 114 patients were included. The annual incidence rate ranged from 0.21 to 0.54%; the perioperative mortality was 2.6%; there were 114 cases of re-operations for hemothorax after 2012, including 62 cases in thoracoscopy group and 52 cases in open group. The durations of chest-tube drainage (7.2 ± 3.9 days vs 10.9 ± 12.0 days, P = 0.001) and length of stay in hospital (13.7 ± 6.7 days vs 18.9 ± 10.6 days, P = 0.002) in the thoracoscopic group were shorter than those in the open group. The thoracoscopic group had fewer post-operative complications as well (P = 0.023). Meanwhile, post-operative complications in the delayed group were significantly higher than those in the non-delayed group, with a longer length of hospital stay and higher hospitalization costs. CONCLUSION: Complete VATS is safe and feasible for re-operation due to post-operative hemothorax and can be an alternative to thoracotomy. Delayed re-operations are associated with more post-operative complications and higher costs.

The IASLC Proposed Grading System Accurately Predicts Prognosis and Mediastinal Nodal Metastasis in Patients With Clinical Stage I Lung Adenocarcinoma.

The International Association for the Study of Lung Cancer (IASLC) recently proposed a new grading system for lung adenocarcinoma (LUAD). We aimed to validate the prognostic performance of the grading system and explore its role in guiding the strategy of lymph node (LN) dissection. We retrospectively reviewed 1029 patients with clinical stage I LUAD who underwent surgery between 2011 and 2013. The association between mediastinal nodal metastasis and grading system was evaluated. To investigate the value of the grading system in guiding LN dissection strategies, 3 pathologists evaluated the feasibility of identifying the grading system using frozen section (FS). The differences in prognosis between all neighboring grades were highly significant based on the grading system ( P <0.001). Notably, almost no grade 1 LUAD (1.4%) had pN2 disease, whereas higher rates were found in grade 2 LUAD (9.6%) and grade 3 LUAD (18.3%) ( P <0.001). Multivariate logistic regression analysis revealed that higher tumor grade was an independent predictor of mediastinal nodal metastasis ( P =0.002). Moreover, limited mediastinal LN dissection had equivalent prognosis in grade 1 LUAD, but significantly worse prognosis in grade 2 and grade 3 LUAD than systematic mediastinal LN dissection. The overall accuracy of using intraoperative FS to identify the IASLC grading system was 85.4% (κ=0.765) with substantial agreement. The IASLC grading system could accurately stratify prognosis and predict mediastinal nodal metastasis in patients with clinical stage I LUAD. FS was feasible for identifying the IASLC grading system.

Reconsidering T component of cancer staging for T3/T4 non-small-cell lung cancer with additional nodule.

Background: Non-small-cell lung cancer (NSCLC) with additional nodule(s) located in the same lobe or ipsilateral different lobe were designated as T3 and T4, respectively, which was merely defined by anatomical location of additional nodule(s), regardless of other prognostic factors. Methods: A total of 4711 patients with T1-4, N0-2, M0 NSCLC undergoing complete resection were identified between 2009 and 2014, including 145 patients with additional nodule(s) in the same lobe (T3-Add) and 174 patients with additional tumor nodule(s) in ipsilateral different lobe (T4-Add). Overall survival (OS) was compared using multivariable Cox regression models and propensity score matching analysis (PSM). Results: T3-Add patients [T3-Add versus T3, hazard ratio (HR), 0.695; 95% confidence interval (CI), 0.528-0.915; p = 0.009] and comparable OS with T2b patients through multivariable Cox analysis, and further validated by PSM. T4-Add patients carried a wide spectrum of prognosis, and the largest diameter of single tumor was screened out as the most effective indicator for distinguishing prognosis. T4-Add (⩽3 cm) patients had better OS than T4 patients [T4-Add (⩽3 cm) versus T4, HR, 0.629; 95% CI, 0.455-0.869; p = 0.005] and comparable OS with T3 patients. And T4-Add (>3 cm) patients had comparable OS with T4 patients. Conclusion: NSCLC patients with additional nodule(s) in the same lobe and ipsilateral different lobe (maximum tumor diameter ⩽ 3 cm) should be further validated and considered restaging as T2b and T3 in the forthcoming 9th tumor, node, and metastasis staging system.

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The stem radius growth of Pinus tabuliformis was monitored by dendrometer during the growing season in 2017 and 2018 at two altitudes (2010 and 2330 m) in the Helan Mountains. We investigated the responses of tree radial growth to drought events. The results showed that drought event in June 2018 reduced stem growth rate of P. tabuliformis. The precipitation in July and August reactivated the stem radius growth. The main growing season of P. tabuliformis stem was June-August in 2018, which was a month longer than that in 2017. The response patterns between stem radial growth of P. tabuliformis and climatic factors were consistent across forest stands in different altitudes. Drought in the early growing season suppressed the radial growth of trees, while precipitation in the mid- and late growing seasons played an important role in promoting the radial growth of trees. The effects of climatic factors in August on tree-ring width should be considered during climate reconstruction in this region.

Origin of Intra-annual Density Fluctuations in a Semi-arid Area of Northwestern China.

Intra-annual density fluctuation (IADF) is a structural modification of the tree ring in response to fluctuations in the weather. The expected changes in monsoon flow would lead to heterogeneous moisture conditions during the growing season and increase the occurrence of IADF in trees of the arid ecosystems of continental Asia. To reveal the timings and physiological mechanisms behind IADF formation, we monitored cambial activity and wood formation in Chinese pine (Pinus tabuliformis) during 2017-2019 at three sites in semi-arid China. We compared the dynamics of xylem formation under a drought event, testing the hypothesis that drought affects the process of cell enlargement and thus induces the production of IADF. Wood microcores collected weekly from April to October were used for anatomical analyses to estimate the timings of cambial activity, and the phases of enlargement, wall thickening, and lignification of the xylem. The first cells started enlargement from late April to early May. The last latewood cells completed differentiation in mid-September. Trees produced IADF in 2018. During that year, a drought in June limited cell production in the cambium, only 36% of the xylem cells being formed in IADF trees, compared to 68% in normal tree rings. IADF cells enlarged under drought in early July and started wall thickening during the rainfall events of late July. The drought restricted cell enlargement and affected wall thickening, resulting in narrow cells with wide walls. Cambium and cell enlargement recovered from the abundant rainfall, producing a new layer with large earlywood tracheids. IADF is a specific adaptation of trees to cope with water deficit events occurring during xylem formation. Our findings confirmed the hypothesis that the June-July drought induces latewood-like IADFs by limiting the process of cell enlargement in the xylem. Our finding suggests a higher occurrence of IADF in trees of arid and semi-arid climates of continental Asia if the changes to monsoon flows result in more frequent drought events during the earlywood formation in June.

Predicted outcomes of subdividing M1-stage metastatic lung cancer based on the prognosis and the response to local consolidative therapy.

BACKGROUND: For stage IV non-small cell lung cancer (NSCLC) patients, systemic therapy is the main strategy, and local consolidative therapy tends to be performed for patients with oligometastases. The porpose of this article is to evaluate the prognostic effects of local consolidative therapy for patients with stage IV NSCLC and divide these patients into different subcategories to stratify the prognoses. METHODS: A total of 30,583 patients with stage IV NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. To identify factors related to high cancer-specific mortality (CSM) rates and compare the prognostic effects of different treatment strategies, a competing risk model was developed. Furthermore, independent prognostic factors identified through multivariable analysis were employed to supplement the current M1 subcategory. Cumulative incidence curves were estimated using the Kaplan-Meier method, and the log-rank test was used to compare prognostic differences. RESULTS: The CSM rates of M1a, M1b, and M1c patients were significantly different [M1b versus M1a: subdistribution hazard ratio (SHR), 1.38; 95% confidence interval (CI), 1.31-1.45; P<0.001; M1c vs. M1a: SHR, 1.76; 95% CI, 1.67-1.85; P<0.001]. Patients were divided into five groups depending on the M1 subcategory and liver involvement (Group A, M1c NSCLC with liver involvement; Group B, M1c NSCLC without liver involvement; Group C, M1b NSCLC with liver involvement; Group D, M1b NSCLC without liver involvement; and Group E, M1a NSCLC). Univariable analysis showed that liver involvement was associated with increased cancer-specific mortality (CSM) rates in both M1b and M1c patients (A vs. B: SHR, 1.36; 95% CI, 1.30-1.43; P<0.001; C vs. D: SHR, 1.27; 95% CI, 1.20-1.35; P<0.001). Primary tumor surgery plus chemotherapy may substantially benefit patients, especially M1b patients (surgery alone: SHR, 0.425; 95% CI, 0.361-0.500; P<0.001 vs. chemotherapy alone: SHR, 0.366; 95% CI, 0.352-0.382; P<0.001 vs. chemotherapy plus surgery: SHR, 0.194; 95% CI, 0.165-0.228; P<0.001; no treatment used as reference). CONCLUSIONS: Subdivision of M1 disease and awareness of liver involvement may help to inform the prognosis of stage IV NSCLC patients and facilitate treatment planning.

Which N Descriptor Is More Predictive of Prognosis in Resected Non-small Cell Lung Cancer: The Number of Involved Nodal Stations or the Location-Based Pathological N Stage?

BACKGROUND: The eighth edition of nodal classification for non-small cell lung cancer (NSCLC) is defined only by the anatomical location of metastatic lymph nodes. RESEARCH QUESTION: We sought to evaluate the prognostic significance and discriminatory capability of the number of involved nodal stations (nS) in a large Chinese cohort. STUDY DESIGN AND METHODS: A total of 4,011 patients with NSCLC undergoing surgical resection between 2009 and 2013 were identified. The optimal cutoff values for nS classification were determined with X-tile software. Kaplan-Meier and multivariate Cox analysis were used to examine the prognostic performance of nS classification in comparison with location-based N classification. A decision curve analysis was performed to evaluate the standardized net benefit of nS classification in predicting prognosis. RESULTS: All the patients were classified into four prognostically different subgroups according to the number of involved nodal stations: (1) nS0 (none positive), (2) nS1 (one involved station), (3) nS2 (two involved stations), and (4) nS ≥ 3 (three or more involved stations). The prognoses among all the neighboring categories of nS classification were statistically significantly different in terms of disease-free survival and overall survival. The multivariate Cox analysis demonstrated that nS was an independent prognostic factor of disease-free survival and overall survival. Patients with N1 or N2 stage disease could be divided into three prognostically different subgroups according to nS classification. However, the prognosis was similar between the N1 and N2 subgroups when patients were staged in the same nS category. The decision curve analysis showed that nS classification tended to have a higher predictive capability than location-based N classification. INTERPRETATION: The nS classification could be used to provide a more accurate prognosis for patients with resected NSCLC. The nS is worth taking into consideration when defining nodal category in the forthcoming ninth edition of the staging system.

UniPortal thoracoscopic pneumonectomy does not compromise perioperative and long-term survival in patients with NSCLC: A retrospective, multicenter, and propensity score matching study.

OBJECTIVES: To compare the perioperative and oncologic outcomes following pneumonectomy performed by uniportal video-assisted thoracoscopic surgery (U-VATS) and thoracotomy in patients with centrally located non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with NSCLC who underwent pneumonectomy at the Shanghai Pulmonary Hospital (SPH) and Sun Yat-sen University Cancer Center (SYUCC) with the U-VATS approach or open approach between 2011 and 2016 were selected. Propensity score matching (1:3) was performed to balance the baseline covariates. Overall survival (OS) rates and recurrence-free survival (RFS) rates were estimated and compared using the Kaplan-Meier method, respectively. RESULTS: The enrollees in the study were 579 patients in the SPH cohort, with 501 (86.5%) in the open group and 48 (13.5%) in the U-VATS group, and 271 patients in the SYUCC cohort, with 245 (90.4%) in the open group and 26 (9.6%) in the U-VATS group. After propensity score matching, morbidity rates and 30-day mortality rates were found to be similar between the U-VATS group and open group in both the SPH and SYUCC cohorts. The long-term OS rate of patients who underwent U-VATS pneumonectomy did not significantly differ compared with the patients who underwent open pneumonectomy in both cohorts (SPH, p = .900; SYUCC, p = .240). Cox regression analysis revealed that the surgical option was not a risk factor for the OS rate (SPH: hazard ratio [HR], 0.925; 95% confidence interval [CI], 0.555 to 1.542; SYUCC: HR, 1.524; 95% CI, 0.752 to 3.087). CONCLUSION: U-VATS can be used to safely perform pneumonectomy in patients with centrally located NSCLC without compromising the perioperative and oncologic outcomes compared with an open approach.

Proposal for Rib invasion as an independent T descriptor for non-small cell lung cancer: A propensity-score matching analysis.

INTRODUCTION: To evaluate the prognosis between patients with non-small cell lung cancer (NSCLC) invading difference depth of chest wall and estimate the impact of rib invasion on the pathological T classifications (pT). METHODS: We retrospectively evaluated 521 patients with resected pT3-4 NSCLC. Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion vs the pT3 and pT4 group). Recurrence-free survival (RFS) and Overall survival (OS) was assessed by Cox regression and Kaplan-Meier methods. Time-dependent receiver operating characteristic (ROC) curves were used to assess the additional benefit for survival prediction after reclassifying rib invasion cases. RESULTS: Chest wall invasion occurred in 171 patients (62 rib invasion, 51 parietal pleural invasion [PL3] and 58 soft tissue invasion). Rib invasion was found to be an independent prognostic factor for both RFS (p = 0.006) and OS (p < 0.001) of pT3-4 NSCLC. The survival of rib invasion group was the worst (RFS: 13.1%; OS: 19.8%), followed by PL3 (RFS: 34.2%, P = 0.001; OS: 48.8%; p < 0.001) and the soft tissue invasion group (RFS: 40.6%, p = 0.001; OS: 57.7%, p < 0.001). Besides, the prognosis of rib invasion group was also found to be worse than those of pT3 (RFS: p < 0.001; OS: p < 0.001) and pT4 group (RFS: p = 0.002; OS: p < 0.001). After PSM, the 5-year RFS rate of rib invasion group were still lower than that of pT3 and pT4 group (p < 0.001); the 5-year OS rate of rib invasion was similar with that of pT4 group (p = 0.066) but lower than that of pT3 group (p = 0.014). The time-dependent ROC curves demonstrated that reclassifying rib invasion as pT4 disease provided an additional benefit for survival prediction (p < 0.001). CONCLUSION: The rib invasion group had a worse prognosis than the PL3 and pT3 groups. The prognostic impact of rib invasion should be further validated as a pT4 disease in the TNM classification.

A new method for predicting survival in stage I non-small cell lung cancer patients: nomogram based on macrophage immunoscore, TNM stage and lymphocyte-to-monocyte ratio.

BACKGROUND: The prognosis of patients with stage I non-small cell lung cancer (NSCLC) is often uncertain. This study aims to investigate a new prognostic tool to classify stage I NSCLC patients more accurately. METHODS: CD68 and CD163 macrophages were quantified by immunohistochemical analyses of the center of the tumor and the invasive margin of the 339 tumors, which were used to construct the macrophage immunoscore (MI). Cox proportional hazards models determined the effects of multiple factors on disease-free survival (DFS) and overall survival (OS). One nomogram was developed to predict DFS and OS of stage I patients. RESULTS: The multivariate Cox analysis identified MI (P<0.001), lymphocyte-to-monocyte ratio (LMR, P=0.006), and TNM stage (P=0.046) as independent prognostic factors for DFS. Compared with MI, TNM stage, and LMR alone, the nomogram improved the prediction accuracy of both DFS and OS in terms of the Harrell concordance index in the training cohort (0.812, P<0.001 for DFS; 0.810, P<0.001 for OS) and the external validation cohort (0.796, P<0.001 for DFS; 0.791, P<0.001 for OS). In addition, net reclassification (Nomogram vs. TNM-stage, P<0.001 for DFS and OS) and the integrated discrimination (Nomogram vs. TNM stage, P<0.001 for DFS and OS) also validated this improvement. CONCLUSIONS: The immunoscore-based prognostic nomogram could effectively predict DFS and OS of stage I NSCLC patients and enhance the predictive value of the TNM stage system.

A modified T categorization for part-solid lesions in Chinese patients with clinical stage I Non-small cell lung cancer.

OBJECTIVES: We evaluated the prognostic impact of the presence of ground glass opacity (GGO) component and compared a modified clinical T categorization (cTm) with the current 8th classification (cT8) for survival prediction in Chinese patients with clinical stage I non-small cell lung cancer (NSCLC). METHODS: According to cTm and cT8 classifications, we retrospectively evaluated 1461 patients with part-solid or pure-solid lesions. The recurrence-free survival (RFS) and overall survival (OS) were analyzed by Kaplan-Meier method and Cox proportional hazard model. The concordance index (C- index), reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were performed to estimate reclassification net benefits of cTm for survival prediction. RESULTS: The cT8 classification clearly stratifies the survival outcomes in solid tumors but not in part-solid tumors. The presence of GGO components was an independent prognostic factor for both RFS and OS (p < 0.001), indicating a better outcome in each clinical T stage. The C-index was significantly improved from 0.650 to 0.730 for RFS (p < 0.001) and 0.647 to 0.730 for OS (p < 0.001) after reclassifying by cTm categorization. The DCA, NRI (RFS: 0.342, OS: 0.302), and IDI (RFS: 0.070, OS: 0.054) demonstrated that the cTm classification provided more net benefit in the survival prediction compared with the current cT8 classification. CONCLUSIONS: The current cT8 classification may not be appropriate for part-solid lesions because the presence of GGO components is associated with excellent prognosis despite clinical stage. Also, the cTm classification for part-solid lesions showed an improvement in survival prediction.

Rhodium catalyzed C-C bond cleavage/coupling of 2-(azetidin-3-ylidene)acetates and analogs.

The C-C bond cleavage/coupling of 2-(azetidin-3-ylidene)acetates with aryl boronic acids catalyzed by a rhodium complex was studied with a "conjugate addition/ß-C cleavage/protonation" strategy.